Crosstalk between cancer‑associated fibroblasts and inflammation in tumor microenvironment: A novel perspective in cancer therapy (Review).

Abstract

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 via 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.