This review proposes a conceptual framework for classifying cancer-associated fibroblasts (CAFs) into conserved molecular phenotypes and distinct spatial archetypes, using single-cell and spatial omics data to link CAF identity to local tissue context.
The framework organizes CAF diversity into two axes — molecular phenotypes (conserved biological states) and spatial archetypes (context-dependent positional identities) — arguing this dual classification better explains how the tumor stroma shapes progression and therapy response.
As a conceptual/review article, the framework lacks direct experimental validation; clinical utility of the proposed classification has not yet been tested in prospective patient cohorts.
Broad stromal-targeting strategies have underperformed; this framework supports a shift toward precision, context-specific CAF modulation. Clinicians should watch for next-generation trials designed around CAF spatial and molecular subtype selection.
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