JAMA Dermatology

<jats:sec><jats:title>Importance</jats:title><jats:p>While UV radiation is a known carcinogen associated with cutaneous squamous cell carcinoma (cSCC), sunburn’s specific role remains less clear.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To quantitatively assess the association between sunburn history and the risk of developing cSCC.</jats:p></jats:sec><jats:sec><jats:title>Data Sources</jats:title><jats:p>A comprehensive search of Embase, PubMed, and Cochrane Library (CENTRAL) was conducted from inception up to May 6, 2025, with no language or date restrictions. Search terms included <jats:italic>Non melanoma skin cancer or nonmelanoma skin cancer or NMSC or squamous cell carcinoma or SCC or cSCC or Bowen disease</jats:italic> and <jats:italic>Sunburn or sun exposure or sunlight or sun damage or ultraviolet radiation or ultraviolet light or ultraviolet rays</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Study Selection</jats:title><jats:p>The study included analytical investigations of the general population that assessed the association between cSCC and any type of sunburn history at any age. The initial screening of 9310 titles and abstracts by 3 masked independent reviewers resulted in 279 articles for full-text review, with 43 ultimately meeting eligibility criteria.</jats:p></jats:sec><jats:sec><jats:title>Data Extraction and Synthesis</jats:title><jats:p>This study follows the Meta-analysis of Observational Studies in Epidemiology (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://www.equator-network.org/reporting-guidelines/meta-analysis-of-observational-studies-in-epidemiology-a-proposal-for-reporting-meta-analysis-of-observational-studies-in-epidemiology-moose-group/">MOOSE</jats:ext-link>) reporting guideline. Two reviewers worked independently to extract relevant data. The random effects DerSimonian-Laird method was used to pool data.</jats:p></jats:sec><jats:sec><jats:title>Main Outcome and Measures</jats:title><jats:p>The main outcome was the risk of developing cSCC. Main measures included sunburn frequency (both undefined and painful, blistering, and/or severe) in any life period, categorized into ordinal variables: none, low, medium, and high. The primary analysis was the most adjusted measure of association, standardized to odds ratio (OR). This incorporated adjusted measures of association when available and unadjusted measures when adjusted measures were absent.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Seventeen studies with a combined 321 473 participants were included in the meta-analysis. Pooled analyses of the most adjusted results revealed significantly increased odds of developing cSCC with medium (OR, 1.51; 95% CI, 1.26-1.81) and high (OR, 1.69; 95% CI, 1.39-2.06) lifetime painful, blistering, and/or severe sunburn frequencies. Similarly, high frequencies of painful, blistering, and/or severe sunburns in childhood were significantly associated with increased cSCC odds (OR, 3.11; 95% CI, 1.26-7.66). A history of any painful, blistering, and/or severe sunburn was also significantly associated with increased odds of cSCC (OR, 1.38; 95% CI, 1.06-1.79).</jats:p></jats:sec><jats:sec><jats:title>Conclusions and Relevance</jats:title><jats:p>This meta-analysis supports an association between painful, blistering, and/or severe sunburns and cSCC.</jats:p></jats:sec>

Global, regional, national prevalence, mortality, and disability-adjusted life-years of cutaneous squamous cell carcinoma and trend analysis from 1990 to 2021 and prediction to 2045.

Front Oncol

The risk of metastases from squamous cell carcinoma of the skin.

Int J Dermatol

Incidence, mortality and trends of cutaneous squamous cell carcinoma in Germany, the Netherlands, and Scotland.

Eur J Cancer

JAMA patient page: suntan and sunburn.

JAMA

Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure.

The landscape of driver mutations in cutaneous squamous cell carcinoma.

NPJ Genom Med

Ultraviolet carcinogenesis in nonmelanoma skin cancer. Part I: incidence rates in relation to geographic locations and in migrant populations.

Skinmed

Ultraviolet carcinogenesis in nonmelanoma skin cancer part II: review and update on epidemiologic correlations.

Host characteristics, sun exposure, indoor tanning and risk of squamous cell carcinoma of the skin.

Int J Cancer

Risk factors for skin cancers: a nested case-control study within the Nurses’ Health Study.

Int J Epidemiol

Lifetime sunburn trajectories and associated risks of cutaneous melanoma and squamous cell carcinoma among a cohort of Norwegian women.

JAMA Dermatol

The ROBINS-I and the NOS had similar reliability but differed in applicability: a random sampling observational studies of systematic reviews/meta-analysis.

J Evid Based Med

Association of tea consumption and cutaneous squamous cell carcinoma.

Nutr Cancer

History of allergy and atopic dermatitis in relation to squamous cell and Basal cell carcinoma of the skin.

Cancer Epidemiol Biomarkers Prev

Case-control study of sun exposure and squamous cell carcinoma of the skin.

Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma.

Arch Dermatol

Risk factors for squamous cell carcinoma of the skin in Saskatchewan, Canada.

J Dermatol Sci

Patterns and timing of sunlight exposure and risk of basal cell and squamous cell carcinomas of the skin–a case-control study.

BMC Cancer

Photosensitizing agents and the risk of non-melanoma skin cancer: a population-based case-control study.

J Invest Dermatol

Patterns of ultraviolet radiation exposure and skin cancer risk: the E3N-SunExp Study.

J Epidemiol

The multicentre south European study ‘Helios’. I: Skin characteristics and sunburns in basal cell and squamous cell carcinomas of the skin.

Br J Cancer

Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case-case-control study.

Predictors for cutaneous basal- and squamous-cell carcinoma among actinically damaged adults.

Skin cancer in a subtropical Australian population: incidence and lack of association with occupation.

Am J Epidemiol

Ultraviolet radiation and risk of cutaneous melanoma and squamous cell carcinoma in males and females in the Norwegian Offshore Petroleum Workers cohort.

Am J Ind Med

Tobacco smoking is associated with cutaneous squamous cell carcinoma but not with basal cell carcinoma or melanoma in adult subjects at risk of skin cancer: a cross-sectional study.

Tob Induc Dis

Meta-analysis in clinical trials revisited.

Contemp Clin Trials

Sunlight exposure, hat use, and squamous cell skin cancer on the head and neck.

J Cutan Med Surg

Known and potential new risk factors for skin cancer in European populations: a multicentre case-control study.

Br J Dermatol

Incidence and determinants of skin cancer in a high-risk Australian population.

A prospective study of incident squamous cell carcinoma of the skin in the nurses’ health study.

J Natl Cancer Inst

Manganese superoxide dismutase polymorphism and risk of skin cancer (United States).

Cancer Causes Control

The p53 codon 72 polymorphism, sunburns, and risk of skin cancer in US Caucasian women.

Mol Carcinog

Genetic variation in XRCC1, sun exposure, and risk of skin cancer.

Sunlight exposure and cutaneous human papillomavirus seroreactivity in basal cell and squamous cell carcinomas of the skin.

J Infect Dis

Gene-environment analyses in a UK Biobank skin cancer cohort identifies important SNPs in DNA repair genes that may help prognosticate disease risk.

Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure.

Epidemiology

The influence of painful sunburns and lifetime sun exposure on the risk of actinic keratoses, seborrheic warts, melanocytic nevi, atypical nevi, and skin cancer.

Prospective study of physical activity and risk of squamous cell carcinoma of the skin.

Occupation and keratinocyte cancer risk: a population-based case-control study.

XPA, haplotypes, and risk of basal and squamous cell carcinoma.

Carcinogenesis

Black tea consumption and risk of skin cancer: an 11-year prospective study.

Caffeine intake and risk of basal cell and squamous cell carcinomas of the skin in an 11-year prospective study.

Eur J Nutr

The influence of the exposome in the cutaneous squamous cell carcinoma, a multicenter case-control study.

Cancers (Basel)

The XRCC1 Arg399Gln polymorphism, sunburn, and non-melanoma skin cancer: evidence of gene-environment interaction.

Cancer Res

Tea consumption and basal cell and squamous cell skin cancer: results of a case-control study.

J Am Acad Dermatol

Risk of basal and squamous cell carcinomas of the skin in Sion, Switzerland: a case-control study.

Tumori

The multicentre south European study ‘Helios’. II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin.

Risk factors for squamous cell carcinoma, a study by the National Dermatology Centre of Colombia.

Actas Dermosifiliogr

A prospective cohort study exploring the joint influence of sunlight exposure and tanning bed use on basal cell carcinoma, squamous cell carcinoma, and melanoma risk.

Arch Dermatol Res

Serum antioxidants and skin cancer risk: an 8-year community-based follow-up study.

History of severe sunburn and risk of skin cancer among women and men in 2 prospective cohort studies.

Long-term ultraviolet flux, other potential risk factors, and skin cancer risk: a cohort study.

A meta-analysis of sunburn and basal cell carcinoma risk.

Cancer Epidemiol

Sunburns and risk of cutaneous melanoma: does age matter? A comprehensive meta-analysis.

Ann Epidemiol

A systematic review of worldwide incidence of nonmelanoma skin cancer.

Validity and reliability of adult recall of past sun exposure in a case-control study of multiple sclerosis.

Development and reliability of a brief skin cancer risk assessment tool.

Cancer Detect Prev

Test-retest of self-reported exposure to artificial tanning devices, self-tanning creams, and sun sensitivity showed consistency.

J Clin Epidemiol

Reproducibility of self-reported melanoma risk factors in a large cohort study of Norwegian women.

Melanoma Res

While UV radiation is a known carcinogen associated with cutaneous squamous cell carcinoma (cSCC), sunburn's specific role remains less clear.
To quantitatively assess the association between sunburn history and the risk of developing cSCC.
A comprehensive search of Embase, PubMed, and Cochrane Library (CENTRAL) was conducted from inception up to May 6, 2025, with no language or date restrictions. Search terms included Non melanoma skin cancer or nonmelanoma skin cancer or NMSC or squamous cell carcinoma or SCC or cSCC or Bowen disease and Sunburn or sun exposure or sunlight or sun damage or ultraviolet radiation or ultraviolet light or ultraviolet rays.
The study included analytical investigations of the general population that assessed the association between cSCC and any type of sunburn history at any age. The initial screening of 9310 titles and abstracts by 3 masked independent reviewers resulted in 279 articles for full-text review, with 43 ultimately meeting eligibility criteria.
This study follows the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. Two reviewers worked independently to extract relevant data. The random effects DerSimonian-Laird method was used to pool data.
The main outcome was the risk of developing cSCC. Main measures included sunburn frequency (both undefined and painful, blistering, and/or severe) in any life period, categorized into ordinal variables: none, low, medium, and high. The primary analysis was the most adjusted measure of association, standardized to odds ratio (OR). This incorporated adjusted measures of association when available and unadjusted measures when adjusted measures were absent.
Seventeen studies with a combined 321 473 participants were included in the meta-analysis. Pooled analyses of the most adjusted results revealed significantly increased odds of developing cSCC with medium (OR, 1.51; 95% CI, 1.26-1.81) and high (OR, 1.69; 95% CI, 1.39-2.06) lifetime painful, blistering, and/or severe sunburn frequencies. Similarly, high frequencies of painful, blistering, and/or severe sunburns in childhood were significantly associated with increased cSCC odds (OR, 3.11; 95% CI, 1.26-7.66). A history of any painful, blistering, and/or severe sunburn was also significantly associated with increased odds of cSCC (OR, 1.38; 95% CI, 1.06-1.79).
This meta-analysis supports an association between painful, blistering, and/or severe sunburns and cSCC.

Sunburn and Cutaneous Squamous Cell Carcinoma: A Meta-Analysis.

Sunburn and Cutaneous Squamous Cell Carcinoma

<jats:sec id="ab-doi250045-4"><jats:title>Importance</jats:title><jats:p>Nicotinamide supplementation has been studied as a chemopreventive medication for reducing skin cancer risk, but large-scale data are limited.</jats:p></jats:sec><jats:sec id="ab-doi250045-5"><jats:title>Objective</jats:title><jats:p>To determine the clinical efficacy of nicotinamide supplementation for skin cancer prevention in the general population and among solid organ transplant recipients.</jats:p></jats:sec><jats:sec id="ab-doi250045-6"><jats:title>Design, Setting, and Participants</jats:title><jats:p>A retrospective cohort study was conducted using electronic health record data (October 1, 1999, to December 31, 2024) from the Veterans Affairs Corporate Data Warehouse (CDW) of 33 822 patients. Analyses were conducted from January 17, 2025, to May 9, 2025. Patients who were exposed to nicotinamide were propensity score matched based on the number and year of skin cancers after which treatment with nicotinamide was initiated, age, sex, self-reported race, exposure to acitretin, exposure to field therapy, history of chronic lymphocytic leukemia, and history of solid organ transplant. The index date was the first prescription of nicotinamide filled within the VA system. Stratified Cox models were used to investigate the association of nicotinamide with skin cancer development.</jats:p></jats:sec><jats:sec id="ab-doi250045-7"><jats:title>Exposures</jats:title><jats:p>Nicotinamide, 500 mg, twice daily for longer than 30 days as documented in the electronic health record.</jats:p></jats:sec><jats:sec id="ab-doi250045-8"><jats:title>Main Outcomes and Measures</jats:title><jats:p>Time to the next skin cancer after baseline.</jats:p></jats:sec><jats:sec id="ab-doi250045-9"><jats:title>Results</jats:title><jats:p>There were 12 287 patients (mean [SD] age, 77.2 [8.9] years; 241 women [2.0%]; 31 [0.3%] American Indian or Alaska Native, 3 [&amp;amp;lt;0.1%] Asian, 13 [0.1%] Black or African American, 59 [0.5%] Native Hawaiian or other Pacific Islander, and 11 662 [94.9%] White individuals) exposed to oral nicotinamide, 500 mg, twice daily for longer than 30 days who were matched to 21 479 unexposed patients (mean [SD] age, 76.9 [8.7] years; 374 women [2.0%]; 49 [0.2%] American Indian or Alaska Native, 3 [&amp;amp;lt;0.1%] Asian, 16 [0.1%] Black or African American, 88 [0.4%] Native Hawaiian or other Pacific Islander, and 20 517 [95.3%] White individuals). Within the matched dataset, there were 10 994 instances of basal cell carcinoma after nicotinamide exposure and 12 551 cutaneous squamous cell carcinoma (cSCC). A total of 1334 (3.9%) in the matched cohort were solid organ transplant recipients. Overall, there was a significant 14% reduction in skin cancer risk. When nicotinamide was initiated after a first skin cancer, the risk reduction rose to 54%, although this benefit declined with initiation following subsequent skin cancers. This risk reduction was seen for skin cancers overall, basal cell carcinoma, and cSCC, with the greatest risk reduction seen for cSCC. Among solid organ transplant recipients, no overall significant risk reduction was observed, although early nicotinamide use was associated with reduced cSCC incidence.</jats:p></jats:sec><jats:sec id="ab-doi250045-10"><jats:title>Conclusions and Relevance</jats:title><jats:p>The results of this cohort study suggest that there is a decreased risk of skin cancer among patients treated with nicotinamide, with the greatest effect seen when initiated after the first skin cancer.</jats:p></jats:sec>

Nicotinamide for keratinocyte carcinoma chemoprevention: a nationwide survey of Mohs surgeons.

Dermatol Surg

A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention.

N Engl J Med

Nicotinamide for skin-cancer chemoprevention in transplant recipients.

Nicotinamide for skin-cancer chemoprevention in transplantation.

Nicotinamide for secondary keratinocyte carcinoma prevention in solid organ transplant recipients.

Frequency and timing of multiple skin cancer development in five cohorts.

Risk of major adverse cardiovascular events following nicotinamide exposure.

Validity of using billing codes from electronic health records to estimate skin cancer counts.

New primary nonmelanoma skin cancer in patients with a history of squamous cell carcinoma of the skin: implications and recommendations for follow-up.

Duration of acceptable delay between the time of diagnosis and treatment of melanoma, cutaneous squamous cell carcinoma and basal cell carcinoma.

J Eur Acad Dermatol Venereol

Development of phenotyping algorithms for the identification of organ transplant recipients: cohort study.

JMIR Med Inform

Effect of nicotinamide in skin cancer and actinic keratoses chemoprophylaxis, and adverse effects related to nicotinamide: a systematic review and meta-analysis.

A bioluminescent-based probe for in vivo non-invasive monitoring of nicotinamide riboside uptake reveals a link between metastasis and NAD+ metabolism.

Biosens Bioelectron

Sirolimus and secondary skin-cancer prevention in kidney transplantation.

Differences in skin cancer rates by transplanted organ type and patient age after organ transplant in White patients.

Risks of multiple skin cancers in organ transplant recipients: a cohort study in 2 administrative data sets.

Timing of subsequent new tumors in patients who present with basal cell carcinoma or cutaneous squamous cell carcinoma.

Consensus-based recommendations on the prevention of squamous cell carcinoma in solid organ transplant recipients: a Delphi consensus statement.

A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients.

Chemoprevention of basal and squamous cell carcinoma with a single course of fluorouracil, 5%, cream: a randomized clinical trial.

Tolerability of high-dose topical tretinoin: the Veterans Affairs Topical Tretinoin Chemoprevention Trial.

Skin cancer in the military: a systematic review of melanoma and nonmelanoma skin cancer incidence, prevention, and screening among active duty and veteran personnel.

Skin cancer risk factors and preventative behaviors among United States military veterans deployed to Iraq and Afghanistan.

Nicotinamide supplementation has been studied as a chemopreventive medication for reducing skin cancer risk, but large-scale data are limited.
To determine the clinical efficacy of nicotinamide supplementation for skin cancer prevention in the general population and among solid organ transplant recipients.
A retrospective cohort study was conducted using electronic health record data (October 1, 1999, to December 31, 2024) from the Veterans Affairs Corporate Data Warehouse (CDW) of 33 822 patients. Analyses were conducted from January 17, 2025, to May 9, 2025. Patients who were exposed to nicotinamide were propensity score matched based on the number and year of skin cancers after which treatment with nicotinamide was initiated, age, sex, self-reported race, exposure to acitretin, exposure to field therapy, history of chronic lymphocytic leukemia, and history of solid organ transplant. The index date was the first prescription of nicotinamide filled within the VA system. Stratified Cox models were used to investigate the association of nicotinamide with skin cancer development.
Nicotinamide, 500 mg, twice daily for longer than 30 days as documented in the electronic health record.
Time to the next skin cancer after baseline.
There were 12 287 patients (mean [SD] age, 77.2 [8.9] years; 241 women [2.0%]; 31 [0.3%] American Indian or Alaska Native, 3 [<0.1%] Asian, 13 [0.1%] Black or African American, 59 [0.5%] Native Hawaiian or other Pacific Islander, and 11 662 [94.9%] White individuals) exposed to oral nicotinamide, 500 mg, twice daily for longer than 30 days who were matched to 21 479 unexposed patients (mean [SD] age, 76.9 [8.7] years; 374 women [2.0%]; 49 [0.2%] American Indian or Alaska Native, 3 [<0.1%] Asian, 16 [0.1%] Black or African American, 88 [0.4%] Native Hawaiian or other Pacific Islander, and 20 517 [95.3%] White individuals). Within the matched dataset, there were 10 994 instances of basal cell carcinoma after nicotinamide exposure and 12 551 cutaneous squamous cell carcinoma (cSCC). A total of 1334 (3.9%) in the matched cohort were solid organ transplant recipients. Overall, there was a significant 14% reduction in skin cancer risk. When nicotinamide was initiated after a first skin cancer, the risk reduction rose to 54%, although this benefit declined with initiation following subsequent skin cancers. This risk reduction was seen for skin cancers overall, basal cell carcinoma, and cSCC, with the greatest risk reduction seen for cSCC. Among solid organ transplant recipients, no overall significant risk reduction was observed, although early nicotinamide use was associated with reduced cSCC incidence.
The results of this cohort study suggest that there is a decreased risk of skin cancer among patients treated with nicotinamide, with the greatest effect seen when initiated after the first skin cancer.

Nicotinamide for Skin Cancer Chemoprevention.

Nicotinamide for Skin Cancer Chemoprevention

British Journal of Dermatology

<jats:title>Abstract</jats:title>
               <jats:sec>
                  <jats:title>Background</jats:title>
                  <jats:p>Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and is caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCCs) which are the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.</jats:p>
               </jats:sec>
               <jats:sec>
                  <jats:title>Objectives</jats:title>
                  <jats:p>To evaluate the antitumour activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator-initiated open-label, single-arm phase II studies were opened in Europe and the USA and enrolled five patients with RDEB diagnosed with locally advanced and/or metastatic SCCs whose disease had not previously responded successfully to standard care.</jats:p>
               </jats:sec>
               <jats:sec>
                  <jats:title>Methods</jats:title>
                  <jats:p>Using a common protocol, patients were offered either oral or intravenous (IV) administration of rigosertib with consultation from the treating physician. Patients were monitored with clinical photography, biopsy, positron emission tomography/computed tomography scans and quality of life (QoL) questionnaires over the 12-month duration of the trial. The pharmacokinetics of drug absorption was monitored in four patients.</jats:p>
               </jats:sec>
               <jats:sec>
                  <jats:title>Results</jats:title>
                  <jats:p>Antitumour efficacy with acceptable toxicity was seen in patients on IV or oral therapy and two patients had a complete response within 6 months of treatment. Their QoL was not negatively impacted by treatment and drug absorption exceeded that seen in previous patient populations presumably due to the relatively high dosing in a cohort of underweight patients.</jats:p>
               </jats:sec>
               <jats:sec>
                  <jats:title>Conclusions</jats:title>
                  <jats:p>These data identify rigosertib as a promising drug therapy for patients with RDEB-SCC where there is a substantial unmet need, absence of approved therapies and where tumours arise on a background of a unique fibrotic and inflammatory environment ­characterized by germline mutations in COL7A1 that promote the development of homogenous primary tumours with aberrant PLK1 ­activity.</jats:p>
                  <jats:p>An author video to accompany this article is available online.</jats:p>
               </jats:sec>

Debra International

DEBRA Austria

Debra of America

Cure EB

Digital

Consensus reclassification of inherited epidermolysis bullosa and other disorders with skin fragility

Clinical characteristics, healthcare use, and annual costs among patients with dystrophic epidermolysis bullosa

Orphanet J Rare Dis

Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986–2006

Cutaneous squamous cell carcinoma in epidermolysis bullosa: a 28-year retrospective study

Acta Derm Venereol

Surgical management and oncological follow-up of cutaneous squamous cell carcinomas arising in epidermolysis bullosa patients

The aggressive behaviour of squamous cell carcinoma in epidermolysis bullosa: analysis of clinical outcomes and tumour characteristics in the Dutch EB Registry

APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa

Sci Transl Med

Fibroblast-derived dermal matrix drives development of aggressive cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa

Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa: best clinical practice guidelines

Variable outcome of immunotherapy in advanced multiple cutaneous squamous cell carcinomas in two patients with recessive dystrophic epidermolysis bullosa

PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma

A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa

Mapping the burden of severe forms of epidermolysis bullosa – implications for patient management

JAAD Int

ON01910, a non-ATP-competitive small molecule inhibitor of PLK1, is a potent anticancer agent

Cancer Cell

Identification of rigosertib for the treatment of recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma

Clin Cancer Res

A small molecule RAS-mimetic disrupts RAS association with effector proteins to block signaling

Cell

Combined effects of PLK1 and RAS in hepatocellular carcinoma reveal rigosertib as promising novel therapeutic ‘dual-hit’ option

Oncotarget

Therapeutic targeting PLK1 by ON-01910.Na is effective in local treatment of retinoblastoma

Oncol Res

Epidemiology and outcome of squamous cell carcinoma in epidermolysis bullosa in Australia and New Zealand

The 2018 European Society of Cardiology/European Society of Hypertension and 2017 American College of Cardiology/American Heart Association blood pressure guidelines: more similar than different

Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline

Quality of life evaluation in epidermolysis bullosa (EB) through the development of the QOLEB questionnaire: an EB-specific quality of life instrument

Type VII collagen deficiency in the oncogenesis of cutaneous squamous cell carcinoma in dystrophic epidermolysis bullosa

Immune disregulation in cutaneous squamous cell carcinoma of patients with recessive dystrophic epidermolysis bullosa: a single pilot study

Life (Basel)

Characteristics and outcomes of squamous cell carcinoma and other cutaneous malignancies in epidermolysis bullosa: a systematic review

Adv Skin Wound Care

Successful use of immunotherapy to treat advanced cutaneous squamous cell carcinoma in recessive dystrophic epidermolysis bullosa

BMJ Case Rep

Induced remission of metastatic squamous cell carcinoma with an immune checkpoint inhibitor in a patient with recessive dystrophic epidermolysis bullosa

Case Rep Oncol

Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3 K and PLK1 pathways, in adult patients with advanced solid malignancies

Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer

Am J Cancer Res

Management of squamous cell carcinoma in a patient with recessive-type epidermolysis bullosa dystrophica

Significance of sentinel node biopsy in the management of squamous cell carcinoma arising from recessive dystrophic epidermolysis bullosa

J Dermatol

PET/CT in the thorax: pitfalls

Radiol Clin North Am

Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography

J Nucl Med

Recessive dystrophic epidermolysis bullosa (RDEB) is an epithelial fragility disease primarily affecting the skin and caused by variants in the COL7A1 gene. Individuals with RDEB are predisposed to develop highly aggressive cutaneous squamous cell carcinomas (SCC) which represent the most common cause of premature death. There is a lack of effective prevention or treatment options for patients with RDEB-SCC.
To evaluate the anti-tumor activity and safety of the polo-like kinase-1 (PLK1) inhibitor, rigosertib, two investigator initiated open-label, single arm phase 2 studies were opened in Europe and the United States and enrolled five RDEB patients diagnosed with locally advanced and/or metastatic SCCs that had failed prior standard of care.
Using a common protocol, patients were offered either oral or intravenous administration of rigosertib with consultation from the treating physician. Patients were monitored with clinical photography, biopsy, PET-CT scans and quality of life questionnaires over the 12 months duration of the trial. Pharmacokinetics of drug absorption was monitored in 4 patients.
Patients on intravenous or oral therapy showed anti-tumor efficacy with acceptable toxicity and two patients had a complete response within six months of treatment. Quality of life was not negatively impacted by treatment and drug absorption exceeded previous patient populations presumably due to the relatively high dosing in an underweight patient cohort.
These data identify rigosertib as a promising drug therapy for RDEB-SCC where there is a substantial unmet need, absence of approved therapies and where tumors arise on the background of a unique fibrotic and inflammatory environment characterized by germline mutations in COL7A1 that promote development of homogenous primary tumors with aberrant PLK1 activity.

Efficacy and Safety of Rigosertib in Patients with Recessive Dystrophic Epidermolysis Bullosa Associated Advanced/Metastatic Cutaneous Squamous Cell Carcinoma.

Efficacy and safety of rigosertib in patients with recessive dystrophic epidermolysis bullosa-associated advanced/metastatic cutaneous squamous cell carcinoma

Photodermatology, Photoimmunology &amp; Photomedicine

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Several widely used drugs have photosensitizing properties, and much research has been conducted to find associations between their use and the risk of developing cutaneous malignant melanoma (cM), basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC), often with conflicting results.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>To assess whether the use of commonly prescribed photosensitizing drugs increases skin cancer risk.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Analyses were performed using a large cohort of women, with prospectively collected information on phenotypic traits and sun exposure. Comprehensive information on pharmaceutical treatments and skin cancer occurrence was obtained through national registries. Drugs with photosensitizing properties were grouped according to the Anatomical Therapeutic Chemical system in nine groups, and associations between the use of such drugs were investigated using multivariable Cox regression analysis. The number of retrieved daily doses was analyzed to test the dose–response relationship.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Hormone replacement therapy significantly increased the risk of BCC (hazard ratio [HR] 1.24; 95% confidence interval [CI]: 1.11–1.39), cSCC (HR 1.23; 95% CI: 1.03–1.47) and cM (HR 1.31; 95% CI: 1.01–1.69), with estrogen driving this risk. There was a trend of increased risk of BCC and cM with higher doses of estrogen treatment. Subgroup analysis among those using diuretics showed that loop diuretics were associated with increased cSCC risk (HR 1.6; 95% CI: 1.3–2.0), including a positive association between risk and dose. Furthermore, increased risks of BCC (HR 1.25; 95% CI: 1.09–1.44) and cM (HR 1.41; 95% CI: 1.03–1.93) were associated with thiazide use. NSAIDs showed a possible curvilinear association to BCC and cSCC.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Estrogen treatment increased the risk of all investigated skin cancers. Among those using diuretics, loop diuretics increased the risk of cSCC, and thiazide use increased the risk of BCC. We suggest that physicians should advise female patients prescribed estrogen, thiazides, or loop diuretics to limit their sun exposure.</jats:p></jats:sec>

Photosensitizing Drugs and Risk of Skin Cancer in Women—A Prospective Population‐Based Study

Cutaneous Squamous Cell Carcinoma in Dermatology Research

Sunburn and Cutaneous Squamous Cell Carcinoma

Nicotinamide for Skin Cancer Chemoprevention

Efficacy and safety of rigosertib in patients with recessive dystrophic epidermolysis bullosa-associated advanced/metastatic cutaneous squamous cell carcinoma

Photosensitizing Drugs and Risk of Skin Cancer in Women—A Prospective Population‐Based Study

Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically Relevant Subgroups of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients

Papers