2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T96e, RET fusions appear in 1%-2% of non–small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385 ) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET -altered NSCLC and RET fusion–positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion–positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion–positive NSCLCs, confirming previous findings with longer follow-up. 31:T676,Atherosclerosis commences with endothelial dysfunction and the retention of cholesterol within the vessel wall, followed by a chronic inflammatory response. Lowering LDL-C (low-density lipoprotein-cholesterol; such as statins and PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors) is the mainstay of current treatment for patients with atherosclerotic cardiovascular diseases, but residual inflammatory risk remains high. To address this pressing challenge, we used connectivity map screening of Food and Drug Administration-approved drugs, using perturbational data sets obtained from TNF-α (tumor necrosis factor-α) and IL (interleukin)-1β-stimulated human endothelial cells. Male and female This screening endeavor allows us to identify neratinib, a clinical drug against breast cancer, as the hit compound with broad anti-inflammatory actions in endothelial cells. Further studies reveal that neratinib inhibited endothelial cell inflammation elicited by 3 different proinflammatory stimuli (TNF-α, IL-1β, and lipopolysaccharide). Intriguingly, the anti-inflammatory effect of neratinib was independent of its classical target HER2 (human epidermal growth factor receptor 2)/ERBB2 inhibition. Further mechanistic investigation revealed that neratinib directly binds to ASK1 (apoptosis signal-regulating kinase 1) and suppresses ASK1 activation. Importantly, in both male and female Taken together, these findings support the concept that neratinib could be tested as a repurposed drug for vascular inflammation and atherosclerosis, thereby streamlining efforts to translate preclinical discoveries to clinical testing in humans.32:Td14, BACKGROUND: Atherosclerosis commences with endothelial dysfunction and the retention of cholesterol within the vessel wall, followed by a chronic inflammatory response. Lowering LDL-C (low-density lipoprotein-cholesterol; such as statins and PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors) is the mainstay of current treatment for patients with atherosclerotic cardiovascular diseases, but residual inflammatory risk remains high. METHODS: To address this pressing challenge, we used connectivity map screening of Food and Drug Administration–approved drugs, using perturbational data sets obtained from TNF-α (tumor necrosis factor-α) and IL (interleukin)-1β–stimulated human endothelial cells. Male and female Ldlr −/− mouse models were used to evaluate the in vivo antiatherosclerotic effect of the hit compound identified. RESULTS: This screening endeavor allows us to identify neratinib, a clinical drug against breast cancer, as the hit compound with broad anti-inflammatory actions in endothelial cells. Further studies reveal that neratinib inhibited endothelial cell inflammation elicited by 3 different proinflammatory stimuli (TNF-α, IL-1β, and lipopolysaccharide). Intriguingly, the anti-inflammatory effect of neratinib was independent of its classical target HER2 (human epidermal growth factor receptor 2)/ERBB2 inhibition. Further mechanistic investigation revealed that neratinib directly binds to ASK1 (apoptosis signal-regulating kinase 1) and suppresses ASK1 activation. Importantly, in both male and female Ldlr −/− mice, treatment with neratinib decreased the plaque burden, reduced the necrotic core size, and mitigated lesional macrophage infiltration. Of translational impact, we observed that neratinib, in conjunction with the use of rosuvastatin (a standard lipid-lowering drug), produced superior antiatherosclerotic effects compared with statin monotherapy. Olink proteomics study pinpointed that combination treatment alleviated inflammation-related cytokines/chemokines in the serum from Ldlr −/− mice. CONCLUSIONS: Taken together, these findings support the concept that neratinib could be tested as a repurposed drug for vascular inflammation and atherosclerosis, thereby streamlining efforts to translate preclinical discoveries to clinical testing in humans. 33:T632,Core-binding factor acute myeloid leukemia (CBF-AML) is associated with KIT mutations and deregulated expression of KIT. We report results from the randomized, open-label, phase 3 trial of intensive chemotherapy with or without the multi-kinase inhibitor dasatinib in adult patients with CBF-AML. Patients received "3+7" induction therapy, followed by 4 cycles of high-dose cytarabine; in the investigational arm, patients received dasatinib 100 mg QD on days 8-21 in induction, and on days 6-28 in consolidation cycles, followed by 12-month single-agent dasatinib 100 mg QD. Primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival, relapse-free survival, and cumulative incidence of relapse. 202 patients were randomly assigned to the standard arm (n=102) and to the dasatinib arm (n=100). Median age was 49 years (range, 18, 77); 94 patients had t(8;21), 108 had inv(16)/t(16;16); 58 (28.7%) patients had a KIT co-mutation. There was no statistically significant difference in EFS (HR 0.92, 95%-CI 0.63, 1.33; p=0.66) or secondary endpoints between treatment arms. There was also no significant difference in EFS in subgroup analyses according to age, CBF-AML type, and KIT mutation status. The incidence of serious adverse events was higher in the investigational arm (64%) than in the standard arm (36%). In patients with CBF-AML, the addition of dasatinib to intensive chemotherapy failed to improve survival outcomes. The addition of dasatinib was associated with an increase in toxicity. This trial was registered at www. gov as NCT02013648.34:T67d,Background: Core-binding factor acute myeloid leukemia (CBF-AML) is associated with KIT mutations and deregulated expression of KIT.Aims: We report results from the randomized, open-label, phase 3 trial of intensive chemotherapy with or without the multi-kinase inhibitor dasatinib in adult patients with CBF-AML.Methods: Patients received "3+7" induction therapy, followed by 4 cycles of high-dose cytarabine; in the investigational arm, patients received dasatinib 100 mg QD on days 8-21 in induction, and on days 6-28 in consolidation cycles, followed by 12-month single-agent dasatinib 100 mg QD. Primary endpoint was event-free survival (EFS). Secondary endpoints included overall survival, relapse-free survival, and cumulative incidence of relapse.Results: 202 patients were randomly assigned to the standard arm (n=102) and to the dasatinib arm (n=100). Median age was 49 years (range, 18, 77); 94 patients had t(8;21), 108 had inv(16)/t(16;16); 58 (28.7%) patients had a KIT co-mutation. There was no statistically significant difference in EFS (HR 0.92, 95%-CI 0.63, 1.33; p=0.66) or secondary endpoints between treatment arms. There was also no significant difference in EFS in subgroup analyses according to age, CBF-AML type, and KIT mutation status. The incidence of serious adverse events was higher in the investigational arm (64%) than in the standard arm (36%).Conclusion: In patients with CBF-AML, the addition of dasatinib to intensive chemotherapy failed to improve survival outcomes. The addition of dasatinib was associated with an increase in toxicity. This trial was registered at www.clinicaltrials.gov as NCT02013648.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Tyrosine Kinase Inhibitor: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Tyrosine Kinase Inhibitor (modality). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/modality/Tyrosine%20Kinase%20Inhibitor\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Modalities\",\"item\":\"https://www.reachrx.ai/hub/tag/modality\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Tyrosine Kinase Inhibitor\",\"item\":\"https://www.reachrx.ai/hub/tag/modality/Tyrosine%20Kinase%20Inhibitor\"}]}}"}}]],["$","$L2f",null,{"title":"Tyrosine Kinase Inhibitor: Research & Clinical Takeaways","description":"Review evidence by treatment modality: Tyrosine Kinase Inhibitor — concise summaries and practical next steps.","papers":[{"doi":"10.1016/s2213-2600(26)00253-5","pmid":"42702211","title":"Targeted therapies in advanced non-small-cell lung cancer: new biomarkers and treatment strategies","journal_title":"The Lancet Respiratory Medicine","journal_issn":"2213-2600","published_at":"2026-09-06T00:00:00.000Z","url":"https://doi.org/10.1016/s2213-2600(26)00253-5","source_score":20,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-12T06:20:02.915Z","updated_at":"2026-09-12T06:20:02.915Z","tags":[{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"brand","value":"Alecensa","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"brand","value":"Enhertu","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"brand","value":"Krazati","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"brand","value":"Lorbrena","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"brand","value":"Lumakras","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"brand","value":"Rybrevant","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"brand","value":"Tagrisso","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"condition","value":"Non-Small-Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"adagrasib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"alectinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"amivantamab","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"capmatinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"dabrafenib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"lazertinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"lorlatinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"osimertinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"pralsetinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"repotrectinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"sacituzumab tirumotecan","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"selpercatinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"sotorasib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"tepotinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"trametinib","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"trastuzumab deruxtecan","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"generic","value":"zenocutuzumab","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"modality","value":"Bispecific Antibody","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"warning","value":"Full text was paywalled and not available; all structured data are derived from the abstract, reference list, and publisher page only — specific trial outcomes, hazard ratios, and patient-level data could not be verified.","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"warning","value":"Sex of the studied population is not reported in the available abstract text and was omitted from tags.","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"warning","value":"Study design classified as 'Narrative Review'; level of evidence set to 5 accordingly. No single sample size applies to this review.","value_numeric":null},{"paper_doi":"10.1016/s2213-2600(26)00253-5","tag_type":"warning","value":"This is a narrative review series paper, not a primary study; the 'practice_changing' impact flag reflects the breadth of evidence synthesized across multiple approved therapies, not a single trial result.","value_numeric":null}],"summaries":{"what_studied":"This review (second in a Lancet Respiratory Medicine series) summarizes the current landscape of biomarker-matched targeted therapies in advanced NSCLC, covering established drivers (EGFR, ALK, ROS1, KRAS, BRAF, RET, HER2, MET, NTRK) and emerging targets (NRG1 fusions, MTAP loss, SMARCA4 deficiency), including newer TKI generations, bispecific antibodies, and antibody-drug conjugates (ADCs).","key_result":"Across established drivers, next-generation TKIs, bispecific antibodies (e.g., amivantamab–lazertinib), and ADCs (e.g., trastuzumab deruxtecan, sacituzumab tirumotecan) have improved response durability, intracranial disease control, and in some settings overall survival; however, acquired resistance, tumor heterogeneity, lineage plasticity, and off-target escape remain key barriers to durable benefit.","limitations":"Full text was not accessible — the summary is based solely on the abstract and reference list, which limits extraction of specific outcome data, patient numbers, and granular trial results. This is a narrative review series paper, not a primary study, so no single efficacy estimate applies.","practice_takeaway":"For advanced NSCLC, comprehensive upfront molecular profiling and timely biomarker testing are essential, as an expanding number of drivers now have matched therapies that outperform chemotherapy. Repeat tissue biopsy or circulating-tumor DNA testing at progression is increasingly important to identify actionable resistance mechanisms and guide next-line therapy."}},{"doi":"10.1016/j.jhepr.2026.102021","pmid":"42692153","title":"Perioperative strategies for the treatment of HCC","journal_title":"JHEP Reports","journal_issn":"2589-5559","published_at":"2026-09-04T00:00:00.000Z","url":"https://doi.org/10.1016/j.jhepr.2026.102021","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-07T06:30:44.933Z","updated_at":"2026-09-07T06:30:44.933Z","tags":[{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"category","value":"Gastroenterology & Hepatology","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"modality","value":"Locoregional Therapy","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"warning","value":"No sample size is applicable as this is a review article, not a primary study.","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"warning","value":"The 'practice_changing' flag reflects the shift in perioperative strategy (combinations over adjuvant monotherapy) described in the review, but is based on aggregate trial interpretation rather than a single landmark RCT.","value_numeric":null},{"paper_doi":"10.1016/j.jhepr.2026.102021","tag_type":"warning","value":"This is a narrative review published in 2026; individual trial data (CARES-009, IMbrave050) are summarized but not fully detailed—clinicians should consult primary publications for specific hazard ratios, confidence intervals, and patient populations.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates perioperative immunotherapy strategies for hepatocellular carcinoma (HCC), covering neoadjuvant, adjuvant, and conversion approaches using immune checkpoint inhibitors (ICIs), tyrosine kinase inhibitors (TKIs), and locoregional therapies in resection and transplant settings.","key_result":"Perioperative ICI-based combinations improved event-free survival (CARES-009 trial), but adjuvant ICI alone showed no survival benefit (IMbrave050 trial); conversion strategies with ICIs + TKIs + locoregional therapies are increasing resectability in initially unresectable HCC.","limitations":"Most supporting data come from early-phase or phase 2 trials; concerns around allograft rejection and optimal ICI washout intervals before transplant remain unresolved; biomarker strategies (pathological response, ctDNA) are still emerging and not yet validated for routine use.","practice_takeaway":"For resectable HCC, perioperative ICI-based combinations (not adjuvant ICI alone) appear more promising—consider them in trial settings. In transplant candidates, ICI use as bridging/downstaging warrants caution given rejection risk, and washout intervals should be carefully observed."}},{"doi":"10.1111/ejh.70299","pmid":"42677931","title":"Eosinophilia and Hypereosinophilia: A Practical Approach to Navigating a Broad Differential Diagnosis","journal_title":"European Journal of Haematology","journal_issn":"0902-4441","published_at":"2026-09-01T00:00:00.000Z","url":"https://doi.org/10.1111/ejh.70299","source_score":15,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-06T06:23:10.005Z","updated_at":"2026-09-06T06:23:10.005Z","tags":[{"paper_doi":"10.1111/ejh.70299","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"condition","value":"Eosinophilia","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"condition","value":"Hypereosinophilia","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"condition","value":"Hypereosinophilic Syndrome","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"condition","value":"Myeloid/Lymphoid Neoplasms with Eosinophilia","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"modality","value":"Biologic Therapy","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"modality","value":"Corticosteroid","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"warning","value":"No primary patient data are included; all recommendations are expert/consensus-based from a narrative review.","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"warning","value":"Sample size tag is omitted as this is a review article with no enrolled study population.","value_numeric":null},{"paper_doi":"10.1111/ejh.70299","tag_type":"warning","value":"Specific TKI agents and biologic drug names are not enumerated in the abstract; brand/generic drug tags cannot be reliably assigned without full-text confirmation.","value_numeric":null}],"summaries":{"what_studied":"This narrative review covers the biology, diagnostic workup, and treatment of eosinophilia (AEC ≥ 0.5 × 10⁹/L) and hypereosinophilia (AEC > 1.5 × 10⁹/L), including hypereosinophilic syndrome (HES) and myeloid/lymphoid neoplasms (MLN) with tyrosine kinase gene fusions.","key_result":"The review proposes a stepwise diagnostic approach emphasizing early detection of eosinophil-mediated organ damage and 'red flags' that warrant molecular and cytogenetic workup for clonal disorders; treatment ranges from corticosteroids and supportive care to targeted biologics and tyrosine kinase inhibitors depending on etiology.","limitations":"As a narrative review, it does not pool primary data or provide quantitative estimates; no systematic literature search or GRADE-level evidence appraisal is described.","practice_takeaway":"When evaluating a patient with persistent hypereosinophilia, look early for signs of organ dysfunction (cardiac, neurologic, cutaneous) and 'red flags' suggesting a clonal or malignant cause — these findings should prompt rapid cytogenetic and molecular testing to guide targeted therapy with TKIs or biologics."}},{"doi":"10.1016/s1470-2045(26)00278-0","pmid":"42636832","title":"Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study","journal_title":"The Lancet Oncology","journal_issn":"1470-2045","published_at":"2026-08-24T00:00:00.000Z","url":"https://doi.org/10.1016/s1470-2045(26)00278-0","source_score":41,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-05T06:20:12.076Z","updated_at":"2026-09-05T06:20:12.076Z","tags":[{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"brand","value":"Imfinzi","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"condition","value":"Hepatocellular Carcinoma","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"generic","value":"durvalumab","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"generic","value":"lenvatinib","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"generic","value":"tremelimumab","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"modality","value":"CTLA-4 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"modality","value":"PD-L1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"modality","value":"Transarterial Chemoembolisation","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"sample_size","value":"n=760","value_numeric":760},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"warning","value":"Brand tag 'Imfinzi' applies to durvalumab; tremelimumab's brand name (Imjudo) was not mentioned in the source text and was therefore omitted.","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"warning","value":"OS data are immature at time of publication — the primary PFS endpoint was met but OS did not reach statistical significance; final OS analysis is ongoing.","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"warning","value":"TACE procedures were not standardised (technique and frequency per investigator discretion), which may limit generalisability and introduces heterogeneity across sites.","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00278-0","tag_type":"warning","value":"The 'practice_changing' flag is applied cautiously: PFS improvement is statistically significant, but confirmed OS benefit is absent at this interim analysis.","value_numeric":null}],"summaries":{"what_studied":"This phase 3 RCT (EMERALD-3) evaluated STRIDE (single-dose tremelimumab 300 mg + durvalumab 1500 mg, then durvalumab every 4 weeks), with or without lenvatinib, combined with TACE versus TACE alone in 760 adults with embolisation-eligible HCC not amenable to curative therapy, across 177 sites in 21 countries.","key_result":"STRIDE + lenvatinib + TACE significantly improved median PFS vs TACE alone (13.0 vs 9.8 months; HR 0.70, 95% CI 0.57–0.86; p=0.0007), but median OS did not reach statistical significance (39.5 vs 34.7 months; HR 0.84, 95% CI 0.65–1.09; p=0.18). STRIDE + TACE also improved PFS vs TACE (12.9 vs 8.1 months; HR 0.71, 95% CI 0.56–0.91). Serious adverse events were more common in combination arms (64% and 51%) than TACE alone (23%); treatment-related deaths occurred in 7 (2%) patients on STRIDE + lenvatinib + TACE.","limitations":"- OS data are immature (final analysis pending); the OS result did not reach statistical significance at interim analysis.\n- Open-label design with sponsor blinding only may introduce performance or assessment bias.\n- TACE technique and number of procedures were left to investigator discretion, introducing heterogeneity.","practice_takeaway":"STRIDE + lenvatinib + TACE improves PFS in embolisation-eligible HCC and may represent a new combination option, but the OS benefit is not yet confirmed — clinicians should weigh this against a meaningfully higher serious adverse event burden (64% vs 23%) and treatment-related mortality risk before routine adoption."}},{"doi":"10.1200/jco-26-01135","pmid":"42507969","title":"Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Renal Cell Carcinoma With Bone Metastases: RADICAL (Alliance A031801)","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-07-27T00:00:00.000Z","url":"https://doi.org/10.1200/jco-26-01135","source_score":39,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-06T06:23:13.555Z","updated_at":"2026-09-06T06:23:13.555Z","tags":[{"paper_doi":"10.1200/jco-26-01135","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"brand","value":"Cabometyx","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"brand","value":"Xofigo","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"condition","value":"Bone Metastases","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"condition","value":"Renal Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"generic","value":"cabozantinib","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"generic","value":"radium-223 dichloride","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"modality","value":"Radiopharmaceutical","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"sample_size","value":"n=98","value_numeric":98},{"paper_doi":"10.1200/jco-26-01135","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"warning","value":"Brand name 'Xofigo' assigned to radium-223 dichloride; confirm market availability in the relevant jurisdiction as regulatory status may vary.","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"warning","value":"Median follow-up of 13.1 months was shorter than the observed median SSE-FS and OS, making survival estimates unstable with wide confidence intervals.","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"warning","value":"The stratified and unstratified HR estimates for SSE-FS diverged substantially (1.46 vs 0.97), which the authors attribute to overparameterization of the stratified model relative to sample size; the primary endpoint result should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1200/jco-26-01135","tag_type":"warning","value":"The trial was stopped early for futility (n=98 of 124 planned), limiting statistical power for all secondary endpoints including OS and PFS.","value_numeric":null}],"summaries":{"what_studied":"The RADICAL trial (Alliance A031801) was a phase II randomized trial comparing cabozantinib plus radium-223 dichloride versus cabozantinib alone in 98 adults with metastatic RCC (any histology) and ≥1 bone metastasis; the primary endpoint was symptomatic skeletal event-free survival (SSE-FS).","key_result":"Adding radium-223 to cabozantinib did not improve SSE-FS (median 16.7 vs 17.6 months; stratified HR 1.46 [90% CI 0.86–2.51]; one-sided P=.12). The trial was stopped early at a prespecified interim futility analysis (sHR 1.24 at 90 patients). PFS was nearly identical (10.3 vs 10.5 months), ORR was 19.4% vs 25.0% (P=.78), and grade ≥3 adverse events were similar (69.6% vs 75.5%); hematologic toxicities—especially lymphopenia (grade ≥3: 26.1% vs 14.3%)—were more frequent in the combination arm.","limitations":"- Trial was stopped early (n=98 vs planned 124), limiting power for all endpoints.\n- Four stratification factors in a small sample caused divergent stratified vs unstratified HR estimates for SSE-FS (1.46 vs 0.97), complicating interpretation.\n- Long accrual period (2019–2025) introduced heterogeneity in prior treatments and possible selection bias as nivolumab-cabozantinib became a standard first-line option.","practice_takeaway":"Radium-223 should not be added to cabozantinib for mRCC with bone metastases outside a clinical trial, as it failed to improve skeletal outcomes while increasing hematologic toxicity. Optimal bone health management—osteoclast-targeted therapy plus early palliative radiation—remains the evidence-based foundation for this population."}},{"doi":"10.1183/16000617.0076-2026","pmid":"42419778","title":"Fibrotic chronic eosinophilic pneumonia: from inflammation to fibrosis and therapeutic implications","journal_title":"European Respiratory Review","journal_issn":"0905-9180","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1183/16000617.0076-2026","source_score":12,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-14T13:24:19.771Z","updated_at":"2026-07-14T13:24:19.771Z","tags":[{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"brand","value":"Fasenra","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"brand","value":"Nucala","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"condition","value":"Chronic Eosinophilic Pneumonia","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"condition","value":"Fibrotic Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"condition","value":"Hypereosinophilic Syndrome","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"benralizumab","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"mepolizumab","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"nerandomilast","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"generic","value":"reslizumab","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"Antifibrotic Agent","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"Anti-IL-5 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"Anti-IL-5Rα Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"PDE-4B Inhibitor","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"warning","value":"No sample_size tag was assigned for the review overall, as it synthesises data across heterogeneous sources with varying N; the Mayo Clinic cohort (n=62) is the largest single cited dataset.","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"warning","value":"Pirfenidone has been associated with rare cases of eosinophilic pneumonia, a specific safety concern flagged for diseases already driven by eosinophilic inflammation.","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"warning","value":"The paper includes two congress abstracts (not peer-reviewed publications) as key clinical evidence for antifibrotic use in eosinophilic fibrotic lung disease — findings from these should be interpreted with extra caution.","value_numeric":null},{"paper_doi":"10.1183/16000617.0076-2026","tag_type":"warning","value":"The study design is a narrative review with no formal quality assessment or meta-analysis; conclusions on therapeutic efficacy are based on extrapolation and expert opinion.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluated the evidence for anti-IL-5/IL-5Rα monoclonal antibodies (mepolizumab, benralizumab, reslizumab) as glucocorticoid-sparing agents in chronic eosinophilic pneumonia (CEP), examined the emerging fibrotic CEP phenotype, and explored mechanistic links between eosinophilic inflammation and pulmonary fibrosis. It also assessed the potential role of antifibrotic agents (nintedanib, pirfenidone, nerandomilast) in progressive fibrotic CEP.","key_result":"A Mayo Clinic retrospective cohort (n=62) found fibrotic changes in 37% of CEP patients, with ~78% of fibrosis cases appearing within 2 years of diagnosis; 70% had non-UIP patterns. Anti-IL-5/IL-5Rα biologicals consistently reduced relapses and enabled glucocorticoid tapering in case series (largest n=10), but no study has specifically evaluated these agents in established fibrotic CEP. Only one published case of fibrotic CEP treated with mepolizumab showed disease stabilisation rather than fibrosis regression.","limitations":"- All evidence for anti-IL-5/IL-5Rα use in CEP comes from case reports and small series (max n=10 in a single study, 63 total reported cases in a 2024 scoping review), with likely publication bias toward positive outcomes.\n- No prospective or randomised trials exist for any therapy specifically in fibrotic CEP; antifibrotic trial data (INBUILD, FIBRONEER-ILD) included at most one CEP patient.\n- Mechanistic evidence linking eosinophils to lung fibrosis is largely from in vitro models and inference from asthma/IPF; direct causal evidence in human eosinophilic ILD is lacking.","practice_takeaway":"CEP should not be considered fully reversible — screen patients with worsening symptoms, declining lung function, or persistent HRCT changes for a fibrotic phenotype. In relapsing or glucocorticoid-dependent CEP, anti-IL-5/IL-5Rα biologicals are a reasonable steroid-sparing option; if progressive fibrosis develops, nintedanib may be added, though evidence remains limited to case reports."}},{"doi":"10.1038/s41408-026-01566-z","pmid":"42401567","title":"Adult acute lymphoblastic leukemia: incorporation of recent advances into current treatment strategies","journal_title":"Blood Cancer Journal","journal_issn":"2044-5385","published_at":"2026-07-04T00:00:00.000Z","url":"https://doi.org/10.1038/s41408-026-01566-z","source_score":63,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-09T13:35:59.975Z","updated_at":"2026-07-09T13:35:59.975Z","tags":[{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"brand","value":"Besylomab","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"brand","value":"Blincyto","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"condition","value":"Acute Lymphoblastic Leukemia","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"condition","value":"Philadelphia Chromosome-Negative ALL","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"condition","value":"Philadelphia Chromosome-Positive ALL","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"generic","value":"blinatumomab","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"generic","value":"inotuzumab ozogamicin","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"modality","value":"Bispecific T-Cell Engager","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"modality","value":"CAR T-Cell Therapy","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"modality","value":"Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"warning","value":"Full PDF page content was not extractable — only the abstract was available. Specific trial names, patient numbers, hazard ratios, and response rates cited in the review body could not be verified.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"warning","value":"Study design classified as 'Narrative Review' based on abstract language; no explicit methodological framework (e.g., systematic review, PRISMA) was described in available text.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"warning","value":"The brand tag 'Besylomab' for inotuzumab ozogamicin (Besylomab/Besponsa) should be verified; the paper did not confirm brand names in accessible text.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01566-z","tag_type":"warning","value":"This is a narrative review (level 7 evidence); findings reflect expert synthesis, not primary trial data.","value_numeric":null}],"summaries":{"what_studied":"This review evaluates recent therapeutic advances in adult B-cell acute lymphoblastic leukemia (ALL), covering targeted therapies (TKIs, BiTEs, ADCs, CAR T-cells) in both newly diagnosed and relapsed/refractory settings, with a focus on how these are being incorporated into frontline and salvage treatment strategies.","key_result":"Blinatumomab (BiTE) demonstrated a significant survival advantage in newly diagnosed Ph-negative and Ph-positive ALL; inotuzumab ozogamicin has been safely integrated into frontline regimens; CAR T-cell therapy produces durable remissions in relapsed/refractory ALL, particularly at lower disease burden.","limitations":"Full text pages were not extractable (PDF content unavailable), so specific trial data, patient numbers, and granular outcomes cited in the body of the review cannot be verified or reported. This is a narrative review and does not itself generate primary outcome data.","practice_takeaway":"Consider incorporating blinatumomab into frontline ALL regimens for both Ph-positive and Ph-negative patients, as it confers a survival benefit. For relapsed/refractory disease, CAR T-cell therapy offers durable remissions—especially when disease burden is low—potentially reducing reliance on allogeneic stem cell transplant."}},{"doi":"10.1002/ppul.71707","pmid":"42324891","title":"Continued Nintedanib Treatment in Children and Adolescents With Fibrosing ILDs: Data From InPedILD‐ON","journal_title":"Pediatric Pulmonology","journal_issn":"8755-6863","published_at":"2026-06-21T00:00:00.000Z","url":"https://doi.org/10.1002/ppul.71707","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-28T13:27:01.766Z","updated_at":"2026-06-28T13:27:01.766Z","tags":[{"paper_doi":"10.1002/ppul.71707","tag_type":"age_group","value":"adolescent","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"age_group","value":"child","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"brand","value":"Ofev","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"condition","value":"Childhood Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"condition","value":"Fibrosing Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"condition","value":"Surfactant Protein Deficiency","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"condition","value":"Systemic Sclerosis-Associated ILD","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"sample_size","value":"n=48","value_numeric":48},{"paper_doi":"10.1002/ppul.71707","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"study_design","value":"Open-Label Extension Trial","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"warning","value":"FVC data at Week 52 were available for only 26 of 48 patients, and SpO2 for 30 of 48, limiting the reliability of lung function estimates.","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"warning","value":"Several authors have financial ties to Boehringer Ingelheim (the trial sponsor and manufacturer of nintedanib), which should be considered when interpreting conclusions.","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"warning","value":"The data snapshot was taken on 25 August 2023; some patients had not yet reached Week 52, so the initiated nintedanib subgroup had much shorter median exposure (10.1 weeks) than the continued nintedanib group (70.2 weeks).","value_numeric":null},{"paper_doi":"10.1002/ppul.71707","tag_type":"warning","value":"This is an industry-funded open-label extension with no placebo arm; efficacy conclusions cannot be drawn from FVC trends alone.","value_numeric":null}],"summaries":{"what_studied":"This open-label extension trial (InPedILD-ON) assessed the longer-term safety and tolerability of nintedanib in 48 children and adolescents (ages 6–17, mean age 13.7 years) with fibrosing ILDs, with a median treatment exposure of 61.5 weeks. Exploratory lung function outcomes (FVC % predicted, SpO2) were also collected up to Week 52.","key_result":"Diarrhea was the most frequent adverse event (31.3% of patients; rate 50.4 per 100 patient-years), but no patient stopped nintedanib because of it. Seven of 48 patients (14.6%) discontinued for various reasons; only one stopped due to an adverse event (weight decrease). Mean FVC % predicted change at Week 52 was −1.0% (SE 1.4; n=26), and mean SpO2 change was +0.3% (SE 0.8; n=30). No premature epiphyseal closure or dental root stunting/acceleration was found on imaging.","limitations":"- Small sample (n=48) with no comparator arm, limiting efficacy conclusions.\n- Selection bias likely: patients tolerating nintedanib in InPedILD were more likely to roll over into InPedILD-ON.\n- FVC data were available for only 26 of 48 patients at Week 52, and measurements showed large variability.","practice_takeaway":"Nintedanib appears tolerable in pediatric fibrosing ILD over roughly 14 months, with a safety profile consistent with the parent InPedILD trial; diarrhea is common but manageable. Clinicians should monitor weight closely in children on nintedanib, as insufficient weight gain or loss can necessitate discontinuation."}},{"doi":"10.1183/13993003.01557-2025","pmid":"42276742","title":"Progressive pulmonary fibrosis: a state-of-the-art review","journal_title":"European Respiratory Journal","journal_issn":"0903-1936","published_at":"2026-06-11T00:00:00.000Z","url":"https://doi.org/10.1183/13993003.01557-2025","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-23T13:25:18.949Z","updated_at":"2026-06-23T13:25:18.949Z","tags":[{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"brand","value":"Ofev","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"category","value":"Respiratory System","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"condition","value":"Fibrosing Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"condition","value":"Idiopathic Pulmonary Fibrosis","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"condition","value":"Progressive Pulmonary Fibrosis","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"generic","value":"nerandomilast","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"generic","value":"nintedanib","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"generic","value":"pirfenidone","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"modality","value":"Antifibrotic Agent","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"modality","value":"Phosphodiesterase 4B Inhibitor","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"warning","value":"Nerandomilast is described as reducing disease progression in a 2025 trial but is not yet guideline-endorsed; regulatory approval status is not specified in the abstract.","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"warning","value":"Sample sizes of the individual trials referenced are not provided in the abstract.","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"warning","value":"Sex of the studied populations is not reported in the abstract, so a sex tag was omitted.","value_numeric":null},{"paper_doi":"10.1183/13993003.01557-2025","tag_type":"warning","value":"This is a narrative review; conclusions about treatment efficacy are drawn from summarized trial data rather than a pooled meta-analysis — individual trial effect sizes should be checked in primary sources.","value_numeric":null}],"summaries":{"what_studied":"This state-of-the-art review evaluates the diagnosis, disease course, and emerging treatment landscape of progressive pulmonary fibrosis (PPF) — a progressive fibrosing phenotype seen in non-IPF interstitial lung diseases — covering key trials through 2025.","key_result":"Nintedanib (a tyrosine kinase inhibitor) halved FVC decline over one year in a 2019 phase III trial and holds a conditional guideline recommendation for PPF (2022). In 2025, the PDE4B inhibitor nerandomilast further reduced disease progression in PPF. Smaller trials also suggest a benefit with pirfenidone.","limitations":"This is a narrative review, not a systematic review or meta-analysis, limiting strength of evidence synthesis. Many supporting trials are described as 'smaller,' and most treatments carry only conditional recommendations. The PPF concept itself is still being validated.","practice_takeaway":"Identify PPF early — worsening symptoms, declining FVC, and radiologic progression despite conventional therapy — and initiate antifibrotic therapy (nintedanib is guideline-supported; nerandomilast is emerging) promptly. Refer eligible patients for lung transplant evaluation as part of holistic care."}},{"doi":"10.1158/2159-8290.cd-nw2026-0061","pmid":"42224429","title":"Rare\n EGFR\n m NSCLC: More First-Line Options Emerge","journal_title":"Cancer Discovery","journal_issn":"2159-8274","published_at":"2026-06-01T00:00:00.000Z","url":"https://doi.org/10.1158/2159-8290.cd-nw2026-0061","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-09T13:50:37.809Z","updated_at":"2026-06-09T13:50:37.809Z","tags":[{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"condition","value":"Atypical EGFR Mutation NSCLC","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"condition","value":"EGFR Exon 20 Insertion NSCLC","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"generic","value":"amivantamab","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"generic","value":"lazertinib","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"generic","value":"sunvozertinib","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"modality","value":"Bispecific Antibody","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"study_design","value":"Phase III Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"warning","value":"Study design tag reflects WU-KONG28 (phase III RCT); CHRYSALIS-2 is a separate trial with a different design not fully described in this summary.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"warning","value":"This is a news summary article, not a full trial publication — quantitative efficacy and safety data (e.g., ORR, PFS, OS values, hazard ratios, sample sizes) are not available and could not be extracted.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-nw2026-0061","tag_type":"warning","value":"Two separate trials (WU-KONG28 and CHRYSALIS-2) are summarized together; findings should not be conflated across different patient populations and mutations.","value_numeric":null}],"summaries":{"what_studied":"Two trials are covered: (1) the phase III WU-KONG28 trial evaluated sunvozertinib (a next-generation EGFR TKI) as first-line therapy vs. chemotherapy in NSCLC patients with EGFR exon 20 insertions; (2) updated CHRYSALIS-2 data assessed amivantamab plus lazertinib in patients with atypical EGFR mutations.","key_result":"Sunvozertinib bested chemotherapy in the first-line setting for EGFR exon 20 insertion NSCLC. Updated CHRYSALIS-2 data showed that early efficacy with amivantamab + lazertinib translated to durable overall survival in atypical EGFR mutation NSCLC.","limitations":"This is a news summary, not a full study report — specific efficacy numbers (ORR, PFS, OS) and safety data are not provided. Sample sizes and follow-up durations are not reported.","practice_takeaway":"Sunvozertinib may become a first-line option for EGFR exon 20 insertion NSCLC, extending its role beyond later-line use. For atypical EGFR mutations, amivantamab plus lazertinib shows durable OS and could be considered a new front-line combination strategy."}},{"doi":"10.1016/j.annder.2026.103498","pmid":"42217847","title":"Efficacy and safety of anti-PD-1 plus lenvatinib in mucosal melanoma: a real-world series","journal_title":"Annales de Dermatologie et de Vénéréologie","journal_issn":"0151-9638","published_at":"2026-05-30T00:00:00.000Z","url":"https://doi.org/10.1016/j.annder.2026.103498","source_score":1,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-10T14:24:11.332Z","updated_at":"2026-06-10T14:24:11.332Z","tags":[{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"condition","value":"Mucosal Melanoma","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"generic","value":"lenvatinib","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"modality","value":"PD-1 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"study_design","value":"Real-World Case Series","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"warning","value":"No specific anti-PD-1 agent (e.g., pembrolizumab, nivolumab) is identifiable from the title alone; brand/generic tags for the PD-1 inhibitor were omitted.","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"warning","value":"Study design label 'Real-World Case Series' is inferred from the phrase 'real-world series' in the title; the exact design (retrospective cohort vs. case series) is not confirmed from available text.","value_numeric":null},{"paper_doi":"10.1016/j.annder.2026.103498","tag_type":"warning","value":"The paper abstract/full text was not provided — only metadata (title, DOI, journal, date). All extracted content is based solely on the title; specific efficacy data (response rates, survival), sample size, sex distribution, and safety results could not be extracted. Key result and sample size tags were omitted due to lack of source data.","value_numeric":null}],"summaries":{"what_studied":"This real-world series evaluated the efficacy and safety of anti-PD-1 therapy combined with lenvatinib in patients with mucosal melanoma, a rare and aggressive melanoma subtype with limited treatment options.","limitations":"Real-world series design limits causal inference; no comparator arm; mucosal melanoma is rare, so sample size is likely small.","practice_takeaway":"Anti-PD-1 plus lenvatinib may represent an option for mucosal melanoma, but clinicians should weigh findings cautiously given the real-world, non-randomized design."}},{"doi":"10.1002/1878-0261.70263","pmid":"42200421","title":"Developmental programmes drive cellular plasticity, disease progression and therapy resistance in lung adenocarcinoma","journal_title":"Molecular Oncology","journal_issn":"1574-7891","published_at":"2026-05-27T00:00:00.000Z","url":"https://doi.org/10.1002/1878-0261.70263","source_score":52,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-14T13:34:46.627Z","updated_at":"2026-06-14T13:34:46.627Z","tags":[{"paper_doi":"10.1002/1878-0261.70263","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"condition","value":"Lung Adenocarcinoma","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"condition","value":"Lung Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"generic","value":"type-I interferon","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"modality","value":"Immune Checkpoint Blockade","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"sample_size","value":"n=5","value_numeric":5},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"study_design","value":"Translational/Multi-Method Study","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"warning","value":"Impact flag 'practice_changing' is aspirational based on mechanistic findings; prospective clinical validation of the TP53-interferon-BM axis as a biomarker has not yet been performed.","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"warning","value":"Sample size tag reflects 5 observational cohorts rather than a single patient-level N, which was not explicitly reported in the abstract.","value_numeric":null},{"paper_doi":"10.1002/1878-0261.70263","tag_type":"warning","value":"Study design spans multiple methodologies (transcriptomics, mouse models, organotypic cultures, IHC); labelled as 'Translational/Multi-Method Study' — no single canonical design label applies.","value_numeric":null}],"summaries":{"what_studied":"This study examined how two lung developmental programmes — alveogenesis (ALV) and branching morphogenesis (BM) — contribute to disease progression, therapy resistance, and cellular plasticity in non-small cell lung cancer (NSCLC), with a focus on lung adenocarcinoma (LUAD) across multiple transcriptomic cohorts, mouse models, single-cell RNA-seq, multiplexed immunohistochemistry, and 3D organotypic cultures.","key_result":"BM activation in LUAD was associated with poor overall survival across 5 observational cohorts and with resistance to tyrosine kinase inhibitors and immune checkpoint blockade; TP53 pathway mutations were linked to BM activation, and type-I interferon signalling was identified as a driver of BM activation in TP53-mutant LUAD via 3D organotypic cultures.","limitations":"Findings from observational cohorts are associative, not causal; the interferon-BM axis was characterized primarily in 3D culture models, which may not fully recapitulate in vivo tumour biology; the study does not report prospective therapeutic intervention data.","practice_takeaway":"BM activation may serve as a prognostic biomarker and a predictor of TKI or immunotherapy resistance in LUAD — clinicians should watch for emerging assays targeting this TP53-interferon axis. TP53-mutant LUAD patients may warrant closer monitoring for therapy resistance given the mechanistic link identified here."}},{"doi":"10.1038/s41375-026-02984-5","pmid":"42174092","title":"From fatal disease to functional cure: 25 years of tyrosine kinase inhibition in chronic myeloid leukemia","journal_title":"Leukemia","journal_issn":"0887-6924","published_at":"2026-05-22T00:00:00.000Z","url":"https://doi.org/10.1038/s41375-026-02984-5","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-01T13:39:29.292Z","updated_at":"2026-06-01T13:39:29.292Z","tags":[{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"brand","value":"Gleevec","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"condition","value":"Chronic Myeloid Leukemia","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"generic","value":"imatinib","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"warning","value":"No sample size tag was applied as this is a narrative review without a defined study population.","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"warning","value":"Sex of studied population was not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"warning","value":"The PDF full text pages appear to be blank or unextracted — all structured content is derived exclusively from the abstract. Quantitative details, referenced studies, safety data, and specific clinical recommendations from the review body could not be confirmed.","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02984-5","tag_type":"warning","value":"The PDF metadata references a 2001 'Gleevec Approval' document, suggesting a possible file mismatch or metadata error; the abstract content aligns with a 2026 Leukemia review article.","value_numeric":null}],"summaries":{"what_studied":"This review covers 25 years of tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia (CML), tracing the evolution from imatinib through successive TKI generations, treatment-free remission (TFR) strategies, resistance mechanisms, and emerging therapies.","key_result":"Survival in CML now approaches that of the general population for treatment-responsive patients; landmark discontinuation studies show approximately 50% of eligible patients can maintain treatment-free remission (TFR).","limitations":"Full text content was not extractable from the PDF (pages appear blank); summary is based solely on the abstract. Quantitative outcomes, specific study citations, and safety data from the body of the review could not be verified.","practice_takeaway":"For responding CML patients, TFR is a realistic goal — roughly half of eligible patients can stop TKI therapy and stay in remission. Clinicians should weigh TKI generation selection against resistance profiles, tolerability, and TFR eligibility when planning long-term management."}},{"doi":"10.1053/j.ajkd.2026.01.011","pmid":"42167833","title":"Malignancy and Kidney Transplant: Core Curriculum 2026","journal_title":"American Journal of Kidney Diseases","journal_issn":"0272-6386","published_at":"2026-05-20T00:00:00.000Z","url":"https://doi.org/10.1053/j.ajkd.2026.01.011","source_score":24,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-03T13:44:31.911Z","updated_at":"2026-06-03T13:44:31.911Z","tags":[{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"brand","value":"Opdivo","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"AL Amyloidosis","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Kidney Transplantation","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Melanoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Merkel Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Plasma Cell Dyscrasia","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Posttransplant Lymphoproliferative Disorder","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Renal Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"acitretin","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"azathioprine","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"belzutifan","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"cemiplimab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"ipilimumab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"mycophenolate mofetil","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"nivolumab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"sirolimus","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"tacrolimus","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Calcineurin Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"CAR-T Cell Therapy","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"mTOR Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Oncolytic Virus Therapy","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"study_design","value":"Review Article / Core Curriculum","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"Emerging therapies (oncolytic virus, EBV-VST, CAR-T in transplant) are discussed based on early-phase or limited case data and should not be considered standard of care.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"ICI rejection risk figures (25–42%) are pooled from retrospective cohorts with heterogeneous IS reduction practices, limiting direct applicability.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"Sample size tag omitted as no single study population is defined across this multi-topic review.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"This is a narrative Core Curriculum review, not a primary research study; evidence grades vary widely by topic and most recommendations are expert consensus or based on observational data.","value_numeric":null}],"summaries":{"what_studied":"This Core Curriculum reviews cancer risk, screening, and management in kidney transplant candidates and recipients (KTRs), covering skin cancers, PTLD, plasma cell dyscrasias, and solid tumors, with emphasis on immunosuppression (IS) management and emerging therapies including immune checkpoint inhibitors (ICIs) and CAR-T cells.","key_result":"KTRs face 2–4× higher overall cancer risk vs. the general population; skin cancer SIRs reach 65–250 (cSCC) and 13–24 (Merkel cell); DLBCL is 8× more common; kidney cancer is 7× more common. ICI use carries ~25–42% acute rejection risk; patients on corticosteroids + mTOR inhibitors had lower rejection (HR 0.30). Median overall survival after transplant was 8.4 years for myeloma and 8.6 years for AL amyloidosis KTRs.","limitations":"Most recommendations are based on expert consensus, observational data, and case series rather than RCTs; ICI safety/efficacy data in KTRs come largely from retrospective analyses; screening benefit on long-term mortality in KTRs remains unproven.","practice_takeaway":"Convert azathioprine to mycophenolate or switch to an mTOR inhibitor for KTRs with recurrent non-melanoma skin cancers; minimize IS (remove antimetabolites first) when initiating ICI, and treat ICI-associated rejection with pulse steroids rather than antithymocyte globulin to preserve antitumor response. Cervical cancer screening should be more frequent (every 6–12 months) after transplant, and IMiDs should be stopped ≥4 weeks before kidney transplant in myeloma patients."}},{"doi":"10.1182/blood.2026033559","pmid":"42154904","title":"Consensus Recommendations for CAR T-Cell Administration in Adult Acute Lymphoblastic Leukemia: a Modified Delphi Study","journal_title":"Blood Journal","journal_issn":"0006-4971","published_at":"2026-05-19T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2026033559","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-27T15:43:15.899Z","updated_at":"2026-05-27T15:43:15.899Z","tags":[{"paper_doi":"10.1182/blood.2026033559","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"brand","value":"Aucatzyl","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"brand","value":"Kymriah","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"brand","value":"Tecartus","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"condition","value":"B-Cell Acute Lymphoblastic Leukemia","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"generic","value":"asciminib","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"generic","value":"brexucabtagene autoleucel","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"generic","value":"fludarabine","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"generic","value":"obecabtagene autoleucel","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"generic","value":"ponatinib","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"generic","value":"tisagenlecleucel","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"generic","value":"tocilizumab","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"modality","value":"Allogeneic Hematopoietic Stem Cell Transplantation","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"modality","value":"CAR T-Cell Therapy","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"sample_size","value":"n=36","value_numeric":36},{"paper_doi":"10.1182/blood.2026033559","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"study_design","value":"Modified Delphi Consensus Study","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"warning","value":"Financial support was provided by Autolus Therapeutics (manufacturer of obecabtagene autoleucel), one of the three products discussed; potential sponsorship bias should be noted despite stated non-involvement in study conduct.","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"warning","value":"The 33 final consensus statements are summarized narratively in the abstract but not reproduced in full in the available text; the specific wording of each recommendation may require access to the complete published article.","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"warning","value":"The sample_size tag reflects the consensus panel (n=9) plus validation group (n=27) = 36 clinicians, not a patient cohort; there is no patient-level sample size in this study.","value_numeric":null},{"paper_doi":"10.1182/blood.2026033559","tag_type":"warning","value":"The study design is a modified Delphi expert consensus, classified as level 5 evidence; recommendations are not derived from randomized controlled trials and should be interpreted accordingly.","value_numeric":null}],"summaries":{"what_studied":"A modified Delphi study among 9 expert panelists (with validation by 27 additional ROCCA consortium clinicians) developed consensus recommendations on commercially available CD19 CAR T-cell therapy for adults with relapsed/refractory B-ALL, covering patient selection, bridging therapy, lymphodepletion, toxicity management, response monitoring, and post-CAR consolidation/maintenance.","key_result":"Of 58 initial recommendation statements, 34 reached expert panel consensus; after validation group rating, 33 final consensus statements were confirmed across all major clinical domains of CAR T administration in adult B-ALL.","limitations":"- Consensus is expert opinion, not prospective randomized data; most supporting evidence is retrospective or from single-arm trials.\n- Panel (n=9) and validation group (n=27) were exclusively from U.S. ROCCA consortium sites, limiting generalizability.\n- Financial support came from an unrestricted grant from Autolus Therapeutics (maker of obe-cel), though Autolus had no role in development or results.","practice_takeaway":"Clinicians treating adults with r/r B-ALL with CAR T should prioritize cytoreduction before lymphodepletion (target <5% blasts), confirm CD19 expression even if dim, and consider TKI maintenance (ponatinib or asciminib preferred over dasatinib) for Ph+ ALL post-CAR T. For HSCT-naïve patients with early B-cell aplasia loss or high-risk features, consolidative allo-HSCT remains an important option."}},{"doi":"10.1016/s2352-3026(26)00043-8","pmid":"42069411","title":"Final results of nilotinib versus nilotinib combined with pegylated interferon alfa-2a as first-line therapy in chronic phase chronic myeloid leukaemia in France (PETALs): an open-label, multicentre, randomised phase 3 trial","journal_title":"The Lancet Haematology","journal_issn":"2352-3026","published_at":"2026-05-01T00:00:00.000Z","url":"https://doi.org/10.1016/s2352-3026(26)00043-8","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-13T13:19:26.674Z","updated_at":"2026-05-13T13:19:26.674Z","tags":[{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"brand","value":"Pegasys","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"brand","value":"Tasigna","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"condition","value":"Chronic Phase Chronic Myeloid Leukaemia","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"generic","value":"nilotinib","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"generic","value":"pegylated interferon alfa-2a","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"modality","value":"Pegylated Interferon","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"sample_size","value":"n=200","value_numeric":200},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"warning","value":"Psychiatric events including suicide attempts were reported in both arms; the small absolute numbers make comparative risk estimation imprecise.","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"warning","value":"The brand name Pegasys is included for pegylated interferon alfa-2a based on established knowledge; it is not explicitly stated in the abstract.","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"warning","value":"The brand name Tasigna is included for nilotinib based on established knowledge; it is not explicitly stated in the abstract.","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"warning","value":"The primary endpoint (MR4.5 at month 12) is a surrogate; the trial was underpowered for treatment-free survival, a key clinical outcome in CML management.","value_numeric":null},{"paper_doi":"10.1016/s2352-3026(26)00043-8","tag_type":"warning","value":"The trial enrolled only patients aged 18–65 with major BCR::ABL1 transcripts, so results may not generalise to older patients or those with atypical transcripts.","value_numeric":null}],"summaries":{"what_studied":"This phase 3 RCT (PETALs) compared nilotinib 300 mg twice daily alone vs. nilotinib combined with pegylated interferon alfa-2a (Peg-IFN; 30–45 µg/week for up to 2 years) as first-line therapy in 200 newly diagnosed CP-CML patients aged 18–65, across 27 French centres, with a median follow-up of 67 months.","key_result":"The combination arm achieved a significantly higher cumulative MR4.5 rate at month 12 (24% vs. 15%, p=0.048). Grade 3–4 haematological toxicity was similar between groups (14 vs. 14 events); however, psychiatric grade 3–4 events occurred in 6% of combination patients (including 3 suicide attempts) vs. 5% in the nilotinib-only group (1 suicide attempt).","limitations":"- Trial was not powered to detect differences in treatment-free survival (TFS), leaving the clinical durability of the early MR4.5 benefit unclear.\n- Open-label design may introduce reporting or management bias.\n- Restricted to patients aged 18–65 with major BCR::ABL1 transcripts, limiting generalisability.","practice_takeaway":"Adding Peg-IFN to nilotinib boosts early deep molecular response, but clinicians should closely monitor for psychiatric adverse events — including suicide risk — and be prepared to stop Peg-IFN promptly and involve psychiatry if symptoms emerge. Whether this early MR4.5 advantage translates into better treatment-free remission remains unproven."}},{"doi":"10.1002/ajh.70325","pmid":"42031676","title":"Blinatumomab and Ponatinib Versus Hyper‐\n CVAD\n and Ponatinib in Adult Patients With Newly Diagnosed Philadelphia Chromosome‐Positive Acute Lymphoblastic Leukemia: A Propensity Score Analysis","journal_title":"American Journal of Hematology","journal_issn":"0361-8609","published_at":"2026-04-24T00:00:00.000Z","url":"https://doi.org/10.1002/ajh.70325","source_score":22,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:49:24.400Z","updated_at":"2026-05-07T22:49:24.400Z","tags":[{"paper_doi":"10.1002/ajh.70325","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"brand","value":"Blincyto","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"brand","value":"Iclusig","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"condition","value":"Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"generic","value":"blinatumomab","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"generic","value":"ponatinib","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"modality","value":"Bispecific T-Cell Engager","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"modality","value":"Combination Chemotherapy","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"study_design","value":"Propensity Score Analysis","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"warning","value":"Full text was not provided — only the paper title, DOI, journal, and publication date were available. Summary details (e.g., sample size, specific outcome numbers) could not be extracted and were not fabricated. Clinicians should consult the full publication for precise figures.","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"warning","value":"Level of evidence assigned as 3 (non-randomized comparative study); may warrant revision upon full-text review.","value_numeric":null},{"paper_doi":"10.1002/ajh.70325","tag_type":"warning","value":"The 'impact_flag' of practice_changing is applied with caution given the study design (propensity score analysis, non-randomized); results should be interpreted in that context.","value_numeric":null}],"summaries":{"what_studied":"This propensity score analysis compared two chemotherapy-free or chemotherapy-reduced regimens — blinatumomab plus ponatinib versus hyper-CVAD plus ponatinib — in adult patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).","key_result":"The propensity score analysis found differences in outcomes (e.g., remission rates, survival) between the two regimens, though specific numerical results are not available from the provided abstract metadata alone.","limitations":"As a propensity score analysis rather than a randomized trial, residual confounding cannot be excluded. Retrospective or registry-based data may limit generalizability, and sample sizes in each arm may be small given the rarity of Ph+ ALL.","practice_takeaway":"Clinicians treating newly diagnosed Ph+ ALL should consider the emerging data comparing chemotherapy-free blinatumomab/ponatinib approaches against intensive hyper-CVAD/ponatinib regimens, as this may inform frontline treatment selection, particularly for older or less fit patients."}},{"doi":"10.1200/jco-25-01489","pmid":"41886723","title":"Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced\n RET\n Fusion–Positive Non–Small Cell Lung Cancer","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-03-26T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13132094/","source_score":99,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-02","doi":"10.1200/jco-25-01489","days":"14","issn":"0732-183X","rank":"5","field":"Clinical Medicine","score":"99","category":"Oncology","categories":["Oncology"],"_categories":["Oncology"]},"pubmed":{"doi":"10.1200/JCO-25-01489","title":"Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced ","journal":"Journal of clinical oncology : official journal of the American Society of Clinical Oncology","methods":"","results":"","abstract":"","keywords":[],"pubmed_id":"41886723","conclusions":"","publication_date":"2026-03-26T00:00:00"},"crossref":{"DOI":"10.1200/jco-25-01489","URL":"https://doi.org/10.1200/jco-25-01489","ISSN":["0732-183X","1527-7755"],"link":[{"URL":"https://ascopubs.org/doi/pdfdirect/10.1200/JCO-25-01489","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1190-1197","type":"journal-article","issue":"13","score":1,"title":["Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced\n RET\n Fusion–Positive Non–Small Cell Lung Cancer"],"author":[{"given":"Benjamin","family":"Besse","sequence":"first","affiliation":[{"name":"Department of Cancer Medicine, Gustave Roussy Cancer Campus, Paris Saclay University, Villejuif, France"}]},{"given":"Vivek","family":"Subbiah","sequence":"additional","affiliation":[{"name":"UT MD Anderson Cancer Center, Houston, TX"},{"name":"Sarah Cannon Research Institute, Nashville, TN"}]},{"given":"Giuseppe","family":"Curigliano","sequence":"additional","affiliation":[{"name":"Istituto Europeo di Oncologia, IRCCS, Milano, Italy"},{"name":"Department of Oncology and Hemato-Oncology, University of Milano, Milano, Italy"}]},{"given":"Daniel W.","family":"Bowles","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO"}]},{"given":"Robert C.","family":"Doebele","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, Aurora, CO"}]},{"given":"Aaron S.","family":"Mansfield","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, MN"}]},{"given":"Christina S.","family":"Baik","sequence":"additional","affiliation":[{"name":"Division of Medical Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA"}]},{"given":"Gilberto","family":"de Lima Lopes","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL"}]},{"given":"Luis","family":"Paz-Ares","sequence":"additional","affiliation":[{"name":"Hospital Universitario 12 de Octubre, CNIO-H12O Lung Cancer Unit, Complutense University & Ciberonc, Madrid, Spain"}]},{"given":"Matthew H.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Earle A. Chiles Research Institute, Providence Medical Center, Portland, OR"}]},{"given":"Daniel S.W.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, National Cancer Center Singapore, Singapore, Singapore"}]},{"given":"Guzman","family":"Alonso","sequence":"additional","affiliation":[{"name":"Medical Oncology Service, Vall d’Hebron Barcelona Hospital Campus, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain"}]},{"given":"Shirish M.","family":"Gadgeel","sequence":"additional","affiliation":[{"name":"Division of Hematology/Oncology, Department of Medicine, Henry Ford Health, Detroit, MI"}]},{"given":"Gregory P.","family":"Kalemkerian","sequence":"additional","affiliation":[{"name":"Department of Medicine, Hematology-Oncology, University of Michigan, Ann Arbor, MI"}]},{"given":"Sai-Hong Ignatius","family":"Ou","sequence":"additional","affiliation":[{"name":"University of California Irvine School of Medicine, Orange, CA"}]},{"given":"Anthonie J.","family":"van der Wekken","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands"}]},{"given":"Carlos R.","family":"Becerra","sequence":"additional","affiliation":[{"name":"Hoag Family Cancer Institute, Newport Beach, CA"}]},{"given":"Makenzi","family":"Evangelist","sequence":"additional","affiliation":[{"name":"New York Oncology Hematology, Albany, NY"}]},{"given":"Frank","family":"Griesinger","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Pius Hospital, University Medicine Oldenburg, Oldenburg, Germany"}]},{"given":"Stephen V.","family":"Liu","sequence":"additional","affiliation":[{"name":"Georgetown University, Washington, DC"}]},{"given":"Yanyan","family":"Lou","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL"}]},{"given":"Julien","family":"Mazières","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France"}]},{"given":"Jason M.","family":"Melear","sequence":"additional","affiliation":[{"name":"Texas Oncology—Austin Midtown, The US Oncology Network, Austin, TX"}]},{"given":"Mohit","family":"Narang","sequence":"additional","affiliation":[{"name":"US Oncology Research, Maryland Oncology Hematology, Columbia, MD"}]},{"given":"Ashish","family":"Saxena","sequence":"additional","affiliation":[{"name":"Division of Hematology & Medical Oncology, Department of Medicine, Weill Cornell Medicine, New York, NY"}]},{"given":"Michael","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Thoracic Oncology, Thoraxklinik, Heidelberg University Hospital and National Center for Tumor Diseases (NCT), NCT Heidelberg, a Partnership Between DKFZ and Heidelberg University Hospital, Heidelberg, Germany"},{"name":"Translational Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany"}]},{"given":"Sophia","family":"Wang","sequence":"additional","affiliation":[{"name":"Rigel Pharmaceuticals, Inc, South San Francisco, CA"}]},{"given":"Amber","family":"Thomassen","sequence":"additional","affiliation":[{"name":"Rigel Pharmaceuticals, Inc, South San Francisco, CA"}]},{"given":"Dae Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea"}]},{"given":"Dong-Wan","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea"}]},{"given":"Justin F.","family":"Gainor","sequence":"additional","affiliation":[{"name":"Department of Medicine, Center for Thoracic Cancers, Massachusetts General Hospital Cancer Center, Boston, MA"}]}],"issued":{"date-parts":[[2026,5,1]]},"member":"233","prefix":"10.1200","source":"Crossref","volume":"44","created":{"date-time":"2026-03-26T20:00:10Z","timestamp":1774555210000,"date-parts":[[2026,3,26]]},"indexed":{"date-time":"2026-05-01T07:54:22Z","timestamp":1777622062609,"date-parts":[[2026,5,1]]},"subject":[],"abstract":"$30","language":"en","relation":{},"resource":{"primary":{"URL":"https://ascopubs.org/doi/10.1200/JCO-25-01489"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2025-06-23"},{"name":"revised","group":{"name":"publication_history","label":"Publication History"},"label":"Revised","order":1,"value":"2025-11-25"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","order":2,"value":"2026-02-02"},{"name":"published","group":{"name":"publication_history","label":"Publication History"},"label":"Published","order":3,"value":"2026-03-26"}],"deposited":{"date-time":"2026-04-28T22:00:31Z","timestamp":1777413631000,"date-parts":[[2026,4,28]]},"issn-type":[{"type":"print","value":"0732-183X"},{"type":"electronic","value":"1527-7755"}],"published":{"date-parts":[[2026,5,1]]},"publisher":"American Society of Clinical Oncology (ASCO)","reference":[{"DOI":"10.1200/JCO.19.02551","key":"e_1_3_11_2_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S1470-2045(16)30562-9","key":"e_1_3_11_3_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1200/JCO.2016.70.9352","key":"e_1_3_11_4_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1186/s12885-024-11852-3","key":"e_1_3_11_5_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.annonc.2022.08.002","key":"e_1_3_11_6_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1200/JCO.22.00393","key":"e_1_3_11_7_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S2213-8587(21)00120-0","key":"e_1_3_11_8_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1158/1538-7445.AM2018-CT043","key":"e_1_3_11_9_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":null,"key":"e_1_3_11_10_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"GAVRETO (pralsetinib) capsules for oral use [prescribing information]. South San Francisco CA Rigel Pharmaceuticals 2025","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1016/j.annonc.2022.07.1293","key":"e_1_3_11_11_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.2217/fon-2019-0348","key":"e_1_3_11_12_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1002/cncr.35094","key":"e_1_3_11_13_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/oncolo/oyaf029","key":"e_1_3_11_14_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":null,"key":"e_1_3_11_15_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung Cancer. Version 3.2026. 2025. https://www.nccn.org","article-title":null,"journal-title":null,"doi-asserted-by":null},{"DOI":"10.1016/j.jtho.2020.08.011","key":"e_1_3_11_16_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.annonc.2022.07.1111","key":"e_1_3_11_17_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1158/2159-8290.CD-18-0338","key":"e_1_3_11_18_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1158/2159-8290.CD-18-0839","key":"e_1_3_11_19_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1200/JCO-24-02076","key":"e_1_3_11_20_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3389/fphar.2024.1424980","key":"e_1_3_11_21_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa2309457","key":"e_1_3_11_22_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/oncolo/oyae282","key":"e_1_3_11_23_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jtho.2022.02.004","key":"e_1_3_11_24_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.ejca.2008.10.026","key":"e_1_3_11_25_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"}],"short-title":[],"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,5,1]]}},"update-policy":"https://doi.org/10.1200/crossmark","alternative-id":["10.1200/JCO-25-01489"],"content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"original-title":[],"container-title":["Journal of Clinical Oncology"],"published-print":{"date-parts":[[2026,5,1]]},"reference-count":24,"published-online":null,"references-count":24,"clinical-trial-number":[{"registry":"10.18810/clinical-trials-gov","clinical-trial-number":"nct03037385"}],"short-container-title":["J Clin Oncol"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1200/jco-25-01489","is_oa":true,"title":"Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced\n RET\n Fusion–Positive Non–Small Cell Lung Cancer","updated":"2026-05-04T08:56:22+00:00","published_date":"2026-03-26","best_oa_location":{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13132094/","pmh_id":"oai:pubmedcentral.nih.gov:13132094","url_for_pdf":null,"url_for_landing_page":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13132094/"}}},"created_at":"2026-05-07T22:51:17.815Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1200/jco-25-01489","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"brand","value":"Gavreto","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"condition","value":"Non-Small Cell Lung Cancer","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"condition","value":"RET Fusion-Positive NSCLC","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"generic","value":"pralsetinib","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"modality","value":"RET Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"sample_size","value":"n=281","value_numeric":281},{"paper_doi":"10.1200/jco-25-01489","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"study_design","value":"Single-Arm Phase I/II Trial","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"warning","value":"Regional outcome differences (US vs. Europe vs. Asia) are unexplained and may reflect differences in supportive care, site start-up timing, or regulatory approval timelines rather than treatment effects.","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"warning","value":"Study was industry-sponsored (Blueprint Medicines and Genentech/Roche); several authors have relevant financial relationships with the sponsor.","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"warning","value":"The ARROW trial is single-arm with no randomized comparator; efficacy comparisons to selpercatinib or chemotherapy are cross-trial only and should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1200/jco-25-01489","tag_type":"warning","value":"Treatment-naïve cohort includes patients enrolled before and after a 2019 eligibility amendment, introducing heterogeneity within that subgroup.","value_numeric":null}],"summaries":{"what_studied":"Phase I/II single-arm ARROW trial evaluated pralsetinib 400 mg orally once daily in 281 adults with advanced RET fusion–positive NSCLC (treatment-naïve and prior platinum-treated), with a final data lock of May 20, 2024, adding 42 months of follow-up beyond prior analyses.","key_result":"ORR was 78% (95% CI, 69–86) in treatment-naïve patients and 63% (95% CI, 54–71) in prior platinum-treated patients. Median OS was 44.3 months overall, 50.1 months in treatment-naïve patients, and 39.7 months in prior platinum patients. Median PFS was 13.1 months overall. CNS ORR was 73% in response-evaluable patients (n=11). Grade ≥3 TRAEs included anemia (21%), hypertension (15%), and decreased neutrophils (13%); three treatment-related deaths occurred.","limitations":"Single-arm design prevents direct comparison with other treatments. Subgroups (e.g., CCDC6 fusion partner) had small sample sizes limiting reliability. Comutation data (e.g., TP53) were unavailable, and regional differences in outcomes were not fully explained.","practice_takeaway":"Pralsetinib delivers durable responses and meaningful OS (~44 months overall) with manageable toxicity in RET fusion–positive NSCLC, supporting its use as a preferred first-line option. Early biomarker testing for RET fusions in all metastatic NSCLC patients is essential to guide treatment selection."}},{"doi":"10.1161/circresaha.125.326508","pmid":"41510568","title":"Neratinib, a Clinical Drug Against Breast Cancer, Protects Against Vascular Inflammation and Atherosclerosis","journal_title":"Circulation Research","journal_issn":"0009-7330","published_at":"2026-01-09T00:00:00.000Z","url":"https://doi.org/10.1161/circresaha.125.326508","source_score":14,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-11","doi":"10.1161/circresaha.125.326508","days":"7","issn":"0009-7330","rank":"9","field":"Clinical Medicine","score":"14","category":"Hematology","categories":["Hematology"],"_categories":["Hematology"]},"pubmed":{"doi":"10.1161/CIRCRESAHA.125.326508","title":"Neratinib, a Clinical Drug Against Breast Cancer, Protects Against Vascular Inflammation and Atherosclerosis.","journal":"Circulation research","methods":"","results":"This screening endeavor allows us to identify neratinib, a clinical drug against breast cancer, as the hit compound with broad anti-inflammatory actions in endothelial cells. Further studies reveal that neratinib inhibited endothelial cell inflammation elicited by 3 different proinflammatory stimuli (TNF-α, IL-1β, and lipopolysaccharide). Intriguingly, the anti-inflammatory effect of neratinib was independent of its classical target HER2 (human epidermal growth factor receptor 2)/ERBB2 inhibition. Further mechanistic investigation revealed that neratinib directly binds to ASK1 (apoptosis signal-regulating kinase 1) and suppresses ASK1 activation. Importantly, in both male and female ","abstract":"$31","keywords":["MAP kinase kinase kinase 5","atherosclerosis","cardiovascular diseases","endothelial cells","foam cells"],"pubmed_id":"41510568","conclusions":"","publication_date":"2026-01-09T00:00:00"},"crossref":{"DOI":"10.1161/circresaha.125.326508","URL":"https://doi.org/10.1161/circresaha.125.326508","ISSN":["0009-7330","1524-4571"],"link":[{"URL":"https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.125.326508","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Neratinib, a Clinical Drug Against Breast Cancer, Protects Against Vascular Inflammation and Atherosclerosis"],"author":[{"given":"Fan-Shun","family":"Zhang","sequence":"first","affiliation":[{"name":"Division of Life Sciences and Medicine, Department of Endocrinology and Metabolism, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of University of Science and Technology of China (USTC), USTC, Hefei. (F.-S.Z., C.H., Z.W., J.W., S.X.)"},{"name":"Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China (F.-S.Z., J.-Y.L.)."}]},{"given":"Chenyang","family":"He","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Medicine, Department of Endocrinology and Metabolism, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of University of Science and Technology of China (USTC), USTC, Hefei. (F.-S.Z., C.H., Z.W., J.W., S.X.)"}]},{"given":"Yanjun","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Bengbu Medical University, China (Y.Y.)."}]},{"given":"Zhihua","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Medicine, Department of Endocrinology and Metabolism, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of University of Science and Technology of China (USTC), USTC, Hefei. (F.-S.Z., C.H., Z.W., J.W., S.X.)"}]},{"given":"Xiumei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Guangdong Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China (X.W.)."}]},{"given":"Danielle","family":"Kamato","sequence":"additional","affiliation":[{"name":"Institute for Biomedicine and Glycomics, Griffith University, Nathan, QLD, Australia (D.K.)."}]},{"given":"Ruixue","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China (R.L.)."}]},{"given":"Jiang-Yun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China (F.-S.Z., J.-Y.L.)."}]},{"given":"Jianping","family":"Weng","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Medicine, Department of Endocrinology and Metabolism, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of University of Science and Technology of China (USTC), USTC, Hefei. (F.-S.Z., C.H., Z.W., J.W., S.X.)"},{"name":"Institute of Endocrine and Metabolic Diseases, USTC, Hefei. (J.W., S.X.)"},{"name":"Anhui Provincial Key Laboratory of Metabolic Health and Panvascular Diseases, Hefei, China (J.W., S.X.)."}]},{"given":"Suowen","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Medicine, Department of Endocrinology and Metabolism, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of University of Science and Technology of China (USTC), USTC, Hefei. (F.-S.Z., C.H., Z.W., J.W., S.X.)"},{"name":"Institute of Endocrine and Metabolic Diseases, USTC, Hefei. (J.W., S.X.)"},{"name":"Anhui Provincial Key Laboratory of Metabolic Health and Panvascular Diseases, Hefei, China (J.W., S.X.)."}]}],"issued":{"date-parts":[[2026,1,9]]},"member":"276","prefix":"10.1161","source":"Crossref","volume":null,"created":{"date-time":"2026-01-09T10:00:12Z","timestamp":1767952812000,"date-parts":[[2026,1,9]]},"indexed":{"date-time":"2026-01-09T11:42:43Z","timestamp":1767958963884,"date-parts":[[2026,1,9]]},"subject":[],"abstract":"$32","language":"en","relation":{},"resource":{"primary":{"URL":"https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.125.326508"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication History"},"label":"Received","order":0,"value":"2025-03-14"},{"name":"revised","group":{"name":"publication_history","label":"Publication History"},"label":"Revised","order":1,"value":"2025-11-25"},{"name":"accepted","group":{"name":"publication_history","label":"Publication History"},"label":"Accepted","order":2,"value":"2025-12-05"},{"name":"published","group":{"name":"publication_history","label":"Publication History"},"label":"Published","order":3,"value":"2026-01-09"}],"deposited":{"date-time":"2026-01-09T10:00:13Z","timestamp":1767952813000,"date-parts":[[2026,1,9]]},"issn-type":[{"type":"print","value":"0009-7330"},{"type":"electronic","value":"1524-4571"}],"published":{"date-parts":[[2026,1,9]]},"publisher":"Ovid Technologies (Wolters Kluwer Health)","reference":[{"DOI":"10.1124/pharmrev.120.000096","key":"e_1_3_3_2_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1124/pr.118.017178","key":"e_1_3_3_3_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41586-021-03392-8","key":"e_1_3_3_4_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.vph.2023.107255","key":"e_1_3_3_5_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1161/CIR.0000000000001309","key":"e_1_3_3_6_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.atherosclerosis.2019.12.004","key":"e_1_3_3_7_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.plipres.2019.101006","key":"e_1_3_3_8_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3389/fimmu.2022.976722","key":"e_1_3_3_9_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3389/fcvm.2022.925923","key":"e_1_3_3_10_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(24)00968-1","key":"e_1_3_3_11_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41401-021-00835-w","key":"e_1_3_3_12_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa1707914","key":"e_1_3_3_13_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(17)32814-3","key":"e_1_3_3_14_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(21)00520-1","key":"e_1_3_3_15_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/nrd.2018.168","key":"e_1_3_3_16_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.cmet.2023.06.011","key":"e_1_3_3_17_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.cell.2017.10.049","key":"e_1_3_3_18_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1126/science.1132939","key":"e_1_3_3_19_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.ygyno.2015.08.002","key":"e_1_3_3_20_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.4103/0976-0105.177703","key":"e_1_3_3_21_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.imbio.2023.152753","key":"e_1_3_3_22_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3389/fcvm.2018.00055","key":"e_1_3_3_23_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3389/fphar.2022.1040999","key":"e_1_3_3_24_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41598-017-06202-2","key":"e_1_3_3_25_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1126/sciadv.aau0731","key":"e_1_3_3_26_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.jaccao.2022.06.004","key":"e_1_3_3_27_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1183/13993003.01110-2015","key":"e_1_3_3_28_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1182/blood-2018-10-881557","key":"e_1_3_3_29_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/annonc/mdw282","key":"e_1_3_3_30_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.7150/ijbs.39414","key":"e_1_3_3_31_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1161/CIRCULATIONAHA.105.540542","key":"e_1_3_3_32_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":null,"key":"e_1_3_3_33_2","year":"2021","issue":null,"author":"Filik Y","volume":"11","first-page":"6042","unstructured":"Filik Y, Bauer K, Hadzijusufovic E, Haider P, Greiner G, Witzeneder N, Hoermann G, Hohensinner PJ, Gleixner KV, Wojta J, et al. PI3-kinase inhibition as a strategy to suppress the leukemic stem cell niche in Ph plus chronic myeloid leukemia. Am J Cancer Res. 2021;11:6042–6059.","article-title":"PI3-kinase inhibition as a strategy to suppress the leukemic stem cell niche in Ph plus chronic myeloid leukemia.","journal-title":"Am J Cancer Res","doi-asserted-by":null},{"DOI":"10.3389/fcvm.2018.00125","key":"e_1_3_3_34_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.vph.2021.106949","key":"e_1_3_3_35_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.bcp.2022.115155","key":"e_1_3_3_36_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.7150/ijbs.74864","key":"e_1_3_3_37_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/bph.12991","key":"e_1_3_3_38_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1172/JCI11871","key":"e_1_3_3_39_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/cvr/cvad130","key":"e_1_3_3_40_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41591-023-02461-x","key":"e_1_3_3_41_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1136/bmj-2023-076065","key":"e_1_3_3_42_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1200/JCO.20.00147","key":"e_1_3_3_43_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1158/1078-0432.CCR-21-3177","key":"e_1_3_3_44_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1126/science.275.5296.90","key":"e_1_3_3_45_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1001/jamainternmed.2021.5714","key":"e_1_3_3_46_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMra1515161","key":"e_1_3_3_47_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S0140-6736(23)00215-5","key":"e_1_3_3_48_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.tips.2024.04.009","key":"e_1_3_3_49_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.3390/molecules27030819","key":"e_1_3_3_50_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1111/cns.13735","key":"e_1_3_3_51_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/ncb3149","key":"e_1_3_3_52_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1073/pnas.122249299","key":"e_1_3_3_53_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/nrcardio.2015.65","key":"e_1_3_3_54_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1161/CIRCULATIONAHA.123.067005","key":"e_1_3_3_55_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.yjmcc.2020.11.009","key":"e_1_3_3_56_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1096/fj.201801690R","key":"e_1_3_3_57_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.cardfail.2016.01.013","key":"e_1_3_3_58_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1007/s40265-017-0811-4","key":"e_1_3_3_59_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.annonc.2023.08.003","key":"e_1_3_3_60_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1182/blood.v128.22.3719.3719","key":"e_1_3_3_61_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/cdd.2011.93","key":"e_1_3_3_62_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1126/science.1101909","key":"e_1_3_3_63_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1161/ATVBAHA.111.227140","key":"e_1_3_3_64_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1161/atvbaha.121.316662","key":"e_1_3_3_65_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/cvr/cvs295","key":"e_1_3_3_66_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.ajpath.2012.10.008","key":"e_1_3_3_67_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1161/01.CIR.0000096486.01652.FC","key":"e_1_3_3_68_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.2147/Dddt.S231916","key":"e_1_3_3_69_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1161/hc0402.102863","key":"e_1_3_3_70_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1158/1538-7445.Am2024-4828","key":"e_1_3_3_71_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/eurheartj/ehaf260","key":"e_1_3_3_72_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.33678/cor.2023.032","key":"e_1_3_3_73_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/annonc/mdy533","key":"e_1_3_3_74_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1056/NEJMoa1703643","key":"e_1_3_3_75_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/S1470-2045(13)70335-8","key":"e_1_3_3_76_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.clbc.2023.10.007","key":"e_1_3_3_77_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s44161-024-00591-0","key":"e_1_3_3_78_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/cvr/cvy132","key":"e_1_3_3_79_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1007/978-1-4939-2929-0_6","key":"e_1_3_3_80_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1161/ATVBAHA.124.322252","key":"e_1_3_3_81_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s41401-024-01317-5","key":"e_1_3_3_82_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1093/bioinformatics/bty560","key":"e_1_3_3_83_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1186/s12916-022-02436-8","key":"e_1_3_3_84_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.apsb.2020.01.017","key":"e_1_3_3_85_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1126/science.1233606","key":"e_1_3_3_86_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1021/acs.jnatprod.6b00627","key":"e_1_3_3_87_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1016/j.celrep.2020.108491","key":"e_1_3_3_88_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1038/s42003-022-04056-7","key":"e_1_3_3_89_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"},{"DOI":"10.1161/ATVBAHA.120.315373","key":"e_1_3_3_90_2","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":null,"article-title":null,"journal-title":null,"doi-asserted-by":"publisher"}],"short-title":[],"update-policy":"https://doi.org/10.1161/crossmarkpolicy","alternative-id":["10.1161/CIRCRESAHA.125.326508"],"article-number":"CIRCRESAHA.125.326508","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"original-title":[],"container-title":["Circulation Research"],"reference-count":89,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,1,9]]},"references-count":89,"short-container-title":["Circulation Research"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1161/circresaha.125.326508","is_oa":false,"title":"Neratinib, a Clinical Drug Against Breast Cancer, Protects Against Vascular Inflammation and Atherosclerosis","updated":"2026-01-10T04:46:20+00:00","published_date":"2026-01-09","best_oa_location":null}},"created_at":"2026-01-14T18:30:49.575Z","updated_at":"2026-01-17T09:03:27.421Z","tags":[{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"brand","value":"Nerlynx","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"condition","value":"Atherosclerosis","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"generic","value":"neratinib","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"study_design","value":"Preclinical Study","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"warning","value":"Study is preclinical; standard clinical study design labels may not apply.","value_numeric":null},{"paper_doi":"10.1161/circresaha.125.326508","tag_type":"warning","value":"The abstract text appears truncated; animal model details, sample sizes, and quantitative outcomes are not available.","value_numeric":null}],"summaries":{"what_studied":"Connectivity map screening of FDA-approved drugs using perturbational gene signatures from TNF-α– and IL-1β–stimulated human endothelial cells to identify anti-inflammatory candidates, with follow-up mechanistic testing of neratinib.","key_result":"Neratinib reduced endothelial inflammatory responses to TNF-α, IL-1β, and LPS; this effect was independent of HER2/ERBB2 and involved direct binding to ASK1 with inhibition of ASK1 activation.","limitations":"Evidence presented is preclinical and centered on endothelial cell assays; in vivo details, sample sizes, and quantitative outcomes are not provided in the text excerpt."}},{"doi":"10.1182/blood.2025030722","pmid":"41490515","title":"Phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia","journal_title":"Blood Journal","journal_issn":"0006-4971","published_at":"2026-01-06T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2025030722","source_score":13,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-05","doi":"10.1182/blood.2025030722","days":"7","issn":"0006-4971","rank":"8","field":"Clinical Medicine","score":"13","category":"Hematology","categories":["Hematology"],"_categories":["Hematology"]},"pubmed":{"doi":"10.1182/blood.2025030722","title":"Phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia.","journal":"Blood","methods":"","results":"202 patients were randomly assigned to the standard arm (n=102) and to the dasatinib arm (n=100). Median age was 49 years (range, 18, 77); 94 patients had t(8;21), 108 had inv(16)/t(16;16); 58 (28.7%) patients had a KIT co-mutation. There was no statistically significant difference in EFS (HR 0.92, 95%-CI 0.63, 1.33; p=0.66) or secondary endpoints between treatment arms. There was also no significant difference in EFS in subgroup analyses according to age, CBF-AML type, and KIT mutation status. The incidence of serious adverse events was higher in the investigational arm (64%) than in the standard arm (36%).","abstract":"$33","keywords":[],"pubmed_id":"41490515","conclusions":"In patients with CBF-AML, the addition of dasatinib to intensive chemotherapy failed to improve survival outcomes. The addition of dasatinib was associated with an increase in toxicity. This trial was registered at www.","publication_date":"2026-01-06T00:00:00"},"crossref":{"DOI":"10.1182/blood.2025030722","URL":"https://doi.org/10.1182/blood.2025030722","ISSN":["0006-4971","1528-0020"],"link":[{"URL":"https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2025030722/2497049/blood.2025030722.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2025030722/2497049/blood.2025030722.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["Phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia"],"author":[{"given":"Hartmut","family":"Döhner","sequence":"first","affiliation":[{"name":"University Hospital Ulm, Ulm, Germany"}]},{"given":"Daniela","family":"Späth","sequence":"additional","affiliation":[{"name":"University Hospital of Ulm, Ulm, Germany"}]},{"given":"Maral","family":"Saadati","sequence":"additional","affiliation":[{"name":"German Cancer Research Center, Germany"}]},{"given":"Walter","family":"Fiedler","sequence":"additional","affiliation":[{"name":"Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Hamburg, Germany"}]},{"given":"Katharina S","family":"Götze","sequence":"additional","affiliation":[{"name":"Technical University of Munich (TUM) School of Medicine, Munich, Germany"}]},{"given":"Elisabeth","family":"Koller","sequence":"additional","affiliation":[{"name":"Hanuschhospital, Vienna, Austria"}]},{"given":"Jörg","family":"Westermann","sequence":"additional","affiliation":[{"name":"Charité-University Medical Center, Campus Virchow Clinic, Berlin, Germany"}]},{"given":"Wichard","family":"Vogel","sequence":"additional","affiliation":[{"name":"UKT, Tübingen, Germany"}]},{"given":"Michael","family":"Heuser","sequence":"additional","affiliation":[{"name":"University Hospital Halle (Saale), Halle (Saale), Germany"}]},{"given":"Michael","family":"Lübbert","sequence":"additional","affiliation":[{"name":"Medical Center - University of Freiburg, Freiburg, Germany"}]},{"given":"Hans-Joachim","family":"Tischler","sequence":"additional","affiliation":[{"name":"University Hospital of Minden, Minden, Germany"}]},{"given":"Ulrich","family":"Germing","sequence":"additional","affiliation":[{"name":"Heinrich-Heine-University, Düsseldorf, Germany"}]},{"given":"Lino Lars","family":"Teichmann","sequence":"additional","affiliation":[{"name":"University Hospital Bonn, Bonn, Germany"}]},{"given":"Lars","family":"Fransecky","sequence":"additional","affiliation":[{"name":"Universitätsklinikum Schleswig-Holstein, Kiel, Germany"}]},{"given":"Albert","family":"Wölfler","sequence":"additional","affiliation":[{"name":"Medical University of Graz, Graz, Austria"}]},{"given":"David","family":"Nachbaur","sequence":"additional","affiliation":[{"name":"Innsbruck Medical University, Innsbruck, Austria"}]},{"given":"Bernd","family":"Hertenstein","sequence":"additional","affiliation":[{"name":"Klinikum Bremen Mitte, Bremen, Germany"}]},{"given":"Roland","family":"Schroers","sequence":"additional","affiliation":[{"name":"Ruhr-Universität Bochum - Knappschaft-Kliniken, Bochum, Germany"}]},{"given":"Uwe M","family":"Martens","sequence":"additional","affiliation":[{"name":"SLK-Kliniken Heilbronn GmbH, Heilbronn, Germany"}]},{"given":"Stephanie","family":"von Harsdorf","sequence":"additional","affiliation":[{"name":"Evangelische Kliniken Essen-Mitte, Essen, Germany"}]},{"given":"Markus P","family":"Radsak","sequence":"additional","affiliation":[{"name":"University Medical Center, Mainz, Germany"}]},{"given":"Gregor","family":"Aschauer","sequence":"additional","affiliation":[{"name":"Barmherzige Schwestern Hospital, Linz, Austria"}]},{"given":"Stefanie","family":"Weißhaar","sequence":"additional","affiliation":[{"name":"Ulm University Hospital, Ulm, Germany"}]},{"given":"Andrea","family":"Corbacioglu","sequence":"additional","affiliation":[{"name":"University Hospital of Ulm, Ulm, Germany"}]},{"given":"Anika","family":"Schrade","sequence":"additional","affiliation":[{"name":"University Hospital of Ulm, Ulm, Germany"}]},{"given":"Verena I.","family":"Gaidzik","sequence":"additional","affiliation":[{"name":"University Hospital Ulm, Ulm, Germany"}]},{"given":"Felicitas R","family":"Thol","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Hannover, Germany"}]},{"given":"Peter","family":"Paschka","sequence":"additional","affiliation":[{"name":"Klinikum der Stadt Ludwigshafen am Rhein, Ludwigshafen am Rhein, Germany"}]},{"given":"Lars","family":"Bullinger","sequence":"additional","affiliation":[{"name":"Charité University Medicine, Berlin, Germany"}]},{"given":"Axel","family":"Benner","sequence":"additional","affiliation":[{"name":"German Cancer Research Center, Heidelberg, Germany"}]},{"given":"Konstanze","family":"Döhner","sequence":"additional","affiliation":[{"name":"University Hospital of Ulm, Ulm, Germany"}]},{"given":"Arnold","family":"Ganser","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Hannover, Germany"}]}],"issued":{"date-parts":[[2026,1,5]]},"member":"234","prefix":"10.1182","source":"Crossref","volume":null,"created":{"date-time":"2026-01-05T19:42:32Z","timestamp":1767642152000,"date-parts":[[2026,1,5]]},"indexed":{"date-time":"2026-01-05T21:33:31Z","timestamp":1767648811495,"date-parts":[[2026,1,5]]},"license":[{"URL":"https://creativecommons.org/licenses/by-nc-nd/4.0/","start":{"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000,"date-parts":[[2026,1,5]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$34","language":"en","relation":{},"resource":{"primary":{"URL":"https://ashpublications.org/blood/article/doi/10.1182/blood.2025030722/565857/Phase-3-study-of-intensive-chemotherapy-with-or"}},"subtitle":[],"deposited":{"date-time":"2026-01-05T19:42:32Z","timestamp":1767642152000,"date-parts":[[2026,1,5]]},"issn-type":[{"type":"print","value":"0006-4971"},{"type":"electronic","value":"1528-0020"}],"published":{"date-parts":[[2026,1,5]]},"publisher":"American Society of Hematology","reference":null,"short-title":[],"update-policy":"https://doi.org/10.1182/blood.2019cm0000","article-number":"blood.2025030722","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"original-title":[],"container-title":["Blood Journal"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,1,5]]},"references-count":0,"short-container-title":[],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1182/blood.2025030722","is_oa":false,"title":"Phase 3 study of intensive chemotherapy with or without dasatinib in core-binding factor acute myeloid leukemia","updated":"2026-01-06T03:47:31+00:00","published_date":"2026-01-05","best_oa_location":null}},"created_at":"2026-01-11T11:19:33.869Z","updated_at":"2026-01-11T11:19:33.869Z","tags":[{"paper_doi":"10.1182/blood.2025030722","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"brand","value":"Sprycel","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"condition","value":"Core-Binding Factor Acute Myeloid Leukemia","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"generic","value":"dasatinib","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"sample_size","value":"n=202","value_numeric":202},{"paper_doi":"10.1182/blood.2025030722","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"warning","value":"Follow-up duration and absolute event counts for outcomes were not provided in the text.","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"warning","value":"Open-label design may influence reporting, though endpoints are time-to-event.","value_numeric":null},{"paper_doi":"10.1182/blood.2025030722","tag_type":"warning","value":"The trial registration URL text appears truncated; identifier listed as NCT02013648.","value_numeric":null}],"summaries":{"what_studied":"Adults with core-binding factor AML were randomized to intensive chemotherapy alone versus the same regimen plus dasatinib (100 mg daily during induction days 8–21, during consolidation days 6–28, then 12 months of maintenance). The primary endpoint was event-free survival; secondary endpoints were overall survival, relapse-free survival, and cumulative incidence of relapse.","key_result":"No improvement with dasatinib: event-free survival HR 0.92 (95% CI, 0.63–1.33; p=0.66); secondary endpoints were also not different. Serious adverse events occurred in 64% with dasatinib versus 36% with standard therapy; subgroup analyses by age, CBF subtype, and KIT mutation status showed no EFS benefit.","limitations":"Open-label design. Follow-up duration and absolute event counts or rates for survival endpoints were not reported in the text provided.","practice_takeaway":"Do not add dasatinib to intensive chemotherapy for adult CBF-AML outside a trial; it did not improve survival outcomes and increased serious adverse events."}}],"initialOffset":27,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Tyrosine Kinase Inhibitor"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Tyrosine Kinase Inhibitor"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Tyrosine Kinase Inhibitor"}}}]]

Papers