Cancer-associated fibroblasts as therapeutic targets for cancer: advances, challenges, and future prospects

Research into cancer treatment has been mainly focused on developing therapies to directly target cancer cells. Over the past decade, extensive studies have revealed critical roles of the tumour microenvironment (TME) in cancer initiation, progression, and drug resistance. Notably, cancer-associated fibroblasts (CAFs) have emerged as one of the primary contributors in shaping TME, creating a favourable environment for cancer development. Many preclinical studies have identified promising targets on CAFs, demonstrating remarkable efficacy of some CAF-targeted treatments in preclinical models. Encouraged by these compelling findings, therapeutic strategies have now advanced into clinical evaluation. We aim to provide a comprehensive review of relevant subjects on CAFs, including CAF-related markers and targets, their multifaceted roles, and current landscape of ongoing clinical trials. This knowledge can guide future research on CAFs and advocate for clinical investigations targeting CAFs.