Journal Article Review Epublish
PubMed: 40755775 DOI: 10.3389/fimmu.2025.1635771
Cancer-associated fibroblasts: dual roles from senescence sentinels to death regulators and new dimensions in therapy.
Front Immunol 16:1635771
Authors: Guixiang Ruan, Xiang Wang, Huiyi Ou, Duancheng Guo
Affiliations
- Department of Radiology, First People's Hospital of Linping District, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, and School of Pharmacy, East China University of Science and Technology, Shanghai, China.
Abstract
Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME), playing a pivotal role in tumor initiation, progression, and therapeutic resistance. This review explores the dual roles of CAFs in regulating tumor cell senescence and cell death, elucidating their mechanisms in inducing cellular senescence, shaping an immunosuppressive milieu, and modulating cell death pathways. CAFs promote tumor progression by secreting pro-inflammatory factors and extracellular matrix (ECM) components, while also contributing to metabolic reprogramming, immune evasion, and therapy resistance, thereby influencing anti-cancer treatment efficacy. Studies indicate that the heterogeneity and plasticity of CAFs determine their distinct functions across various tumor types. Consequently, precision-targeted therapeutic strategies against CAFs, including the elimination of senescent CAFs, inhibition of the senescence-associated secretory phenotype (SASP), and disruption of CAF-mediated cell death evasion mechanisms, have emerged as promising directions in cancer research. This review provides a comprehensive analysis of CAFs functions and their potential as therapeutic targets, offering valuable insights into the development of novel anti-cancer strategies.
MeSH
Cells, Neoplasms, Cellular Senescence, Cancer-Associated Fibroblasts, Fibroblasts, Therapeutics, Cell Death