Liu Xinyan, Wang Chaofeng, Mao Huijuan, Wei Jianzi
School of Acupuncture‑Moxibustion and Tuina, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China.
Oncol Rep. 2025 Aug;54(2). doi: 10.3892/or.2025.8926. Epub 2025 Jun 13.
Inflammation is a hallmark of cancer, significantly contributing to tumor progression and therapeutic outcomes. Among the diverse cellular components of the tumor microenvironment, fibroblasts have been recognized as key regulators of inflammatory processes. Under tumor‑specific conditions, cancer‑associated fibroblasts (CAFs) undergo differentiation and promote tumor proliferation, metastasis and immune evasion highly intricate mechanisms. This review provides a comprehensive analysis of the reciprocal interactions between CAFs and inflammation, elucidating the mechanisms by which CAFs induce pro‑inflammatory signaling and how inflammatory mediators, in turn, potentiate CAF activation and function. Furthermore, innovative therapeutic strategies, including the inhibition of stromal proteins, hypoxia‑inducible factor 1α and metabolic pathways associated with CAFs, as well as the application of nanoparticle‑based drug delivery systems, are examined for their potential to impede CAF‑mediated tumor progression. Pharmacological agents targeting CAF‑associated signaling pathways or inflammatory cytokines show dual efficacy by concurrently modulating inflammatory responses and CAF activity. These approaches frequently demonstrate improved therapeutic efficacy compared to interventions solely directed at CAF surface proteins, highlighting the therapeutic potential of concurrently addressing both inflammation and CAFs to enhance cancer treatment efficacy.
炎症是癌症的一个标志，对肿瘤进展和治疗结果有重大影响。在肿瘤微环境的多种细胞成分中，成纤维细胞已被认为是炎症过程的关键调节因子。在肿瘤特异性条件下，癌症相关成纤维细胞（CAFs）发生分化，并通过高度复杂的机制促进肿瘤增殖、转移和免疫逃逸。本综述全面分析了CAFs与炎症之间的相互作用，阐明了CAFs诱导促炎信号的机制以及炎症介质如何反过来增强CAF的激活和功能。此外，还研究了包括抑制基质蛋白、缺氧诱导因子1α和与CAFs相关的代谢途径，以及应用基于纳米颗粒的药物递送系统等创新治疗策略，以探讨其阻碍CAF介导的肿瘤进展的潜力。靶向CAF相关信号通路或炎性细胞因子的药物通过同时调节炎症反应和CAF活性显示出双重疗效。与仅针对CAF表面蛋白的干预措施相比，这些方法常常表现出更高的治疗效果，突出了同时解决炎症和CAFs以提高癌症治疗效果的治疗潜力。
