Masuda Hideyuki
Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University, Tokyo, Japan.
Cell Death Discov. 2025 Jul 24;11(1):341. doi: 10.1038/s41420-025-02566-x.
Although cancer treatment saves many lives, some types of cancer, such as pancreatic ductal adenocarcinoma (PDAC), exhibit therapeutic resistance and continue to show high mortality. Tumors in cancers such as PDAC contain a substantial amount of cancer-associated fibroblast (CAF)-secreted collagen and other extracellular matrix (ECM) components, which significantly contribute to cancer therapeutic resistance. In the tumor microenvironment, CAFs stabilize the tissue by producing ECM components, remodel ECM through degradation, induce metastasis through epithelial-mesenchymal transition, and suppress cancer immune responses. Recent advances in single-cell analysis have gradually elucidated the subtypes of CAFs and their functions, leading to the emergence of CAF-targeting therapeutic strategies. In this review, I provide an overview of CAFs, their functions and classifications, the mechanisms underlying their role in therapeutic resistance, and the current status of CAF-targeting therapeutic strategies. Moreover, I explored how we can advance cancer treatment by leveraging our understanding of CAFs.
尽管癌症治疗挽救了许多生命,但某些类型的癌症,如胰腺导管腺癌(PDAC),表现出治疗抗性,死亡率仍然很高。在诸如PDAC等癌症中,肿瘤含有大量癌症相关成纤维细胞(CAF)分泌的胶原蛋白和其他细胞外基质(ECM)成分,这显著促成了癌症治疗抗性。在肿瘤微环境中,CAF通过产生ECM成分来稳定组织,通过降解重塑ECM,通过上皮-间质转化诱导转移,并抑制癌症免疫反应。单细胞分析的最新进展逐渐阐明了CAF的亚型及其功能,从而催生了针对CAF的治疗策略。在这篇综述中,我概述了CAF、它们的功能和分类、它们在治疗抗性中发挥作用的潜在机制,以及针对CAF的治疗策略的现状。此外,我探讨了如何通过利用我们对CAF的了解来推进癌症治疗。