Transforming role of cancer associated fibroblasts: From therapeutic barriers to promising targets

Tumor microenvironment (TME) serves as a critical mediator in cancer progression and treatment response, with cancer-associated fibroblasts (CAFs) recognized as core regulators of stromal-tumor interactions. As essential components of the TME, CAFs orchestrate tumor progression and therapy resistance through multifaceted mechanisms, including extracellular matrix (ECM) remodeling, angiogenesis modulation, and immune regulation, which collectively establish a complex regulatory network. Owing to their functional heterogeneity and potent tumor-promoting properties, CAFs have emerged as promising targets for novel anti-tumor therapies. This review highlights recent advances in the understanding of CAFs, focusing on their intricate interactions within the TME and their synergistic roles in promoting therapy resistance in cancer. Furthermore, we also discuss current CAF-targeted therapeutic strategies and ongoing clinical trials, and propose future research directions to further advance this field.