CAF Heterogeneity in Ovarian Cancer: Implications for Chemoresistance and Treatment Strategies.

作者：S. Gopinath, P. Balakrishnan, Yamini Muli, Jubilee Ramasamy, Saranya Puniyakotti, Nithya Varadarajan, R. Velmurugan · 发表于：Anti-Cancer Agents in Medicinal Chemistry · 年份：2026 · DOI：10.2174/0118715206434395260409095604 · 研究领域：Medicine

INTRODUCTION Cancer-Associated Fibroblasts (CAFs) are key players in the tumor microenvironment (TME) of ovarian cancer, influencing progression and chemoresistance. Their heterogeneous subtypes contribute distinctly to immune evasion, extracellular matrix (ECM) remodelling, and drug resistance. METHODS This review synthesizes evidence from recent single-cell and proteomic analyses to delineate CAF subtypes, including myCAFs, iCAFs, and apCAFs, and their associated gene signatures (e.g., VCAN, SULF1, COL11A1, CXCL12). The relationship between CAF-mediated pathways and resistance to platinum-based chemotherapies is explored. RESULTS High expression of CAF-associated genes correlates with platinum resistance in ovarian cancer. VCAN enhances ECM stiffness and immune suppression; SULF1 alters ECM sulfation, affecting drug uptake; COL11A1 activates Src/Akt pathways leading to EMT; and CXCL12 triggers Wnt/β-catenin signalling, increasing resistance. These mechanisms collectively impair treatment efficacy. DISCUSSION The dynamic and plastic nature of CAFs presents both a challenge and an opportunity in cancer therapy. While some CAF subsets promote chemoresistance, others may exert tumor-suppressive effects. This duality underscores the importance of precise molecular profiling to distinguish between pro-tumor and antitumor CAF populations. Current data suggest that therapeutic approaches targeting CAF-specific genes or pathways, particularly those influencing ECM remodelling ...