肿瘤进展中的衰老肿瘤相关成纤维细胞：从形成到治疗机会

Cancer-associated fibroblasts (CAFs) are a key cellular component of the tumor microenvironment (TME), which comprises distinct subtypes, each exhibiting unique and significant roles in cancer development. Senescent cancer-associated fibroblasts (senCAFs) are a newly identified subset of CAFs characterized by high expression of senescence-associated markers.

Notably, senCAFs significantly promote tumor malignancy through the secretion of diverse senescence-associated secretory phenotype (SASP) factors, such as interleukin-6 (IL-6), interleukin-8 (IL-8), matrix metalloproteinases (MMPs), and transforming growth factor- (TGF- ), thereby facilitating tumor cell proliferation, invasion, angiogenesis, immunosuppression, and resistance to cancer therapy.

Consequently, targeting senCAFs-either through selective clearance of this cell subset or suppression of their SASP-represents a promising approach for cancer treatment. Emerging therapies include pharmacological inhibition of key SASP regulatory pathways (e. g. , JAK/STAT3 and NF- B) and antagonists targeting individual SASP components.

Additionally, senolytic agents and therapies targeting senCAF-specific markers (e. g. , TSPAN8) are being actively explored.

Furthermore, immunotherapies, including CAR-T cells targeting senescence-associated surface proteins, provide intriguing avenues. These advances highlight senCAFs as attractive therapeutic targets and underscore the potential for integrating SASP inhibitors and senolytic agents into precision oncology paradigms.