Bridging the tumor microenvironment: the pivotal role of cancer-associated fibroblasts in tumor cachexia development

Tumor cachexia represents a complex and multifaceted metabolic syndrome that profoundly affects the quality of life and survival rates of individuals. It is highly prevalent in advanced cancer patients and is characterized by severe weight loss, muscle wasting, and systemic inflammation. The tumor microenvironment (TME) is pivotal in cancer formation and progression, where cancer-associated fibroblasts (CAFs) emerge as significant contributors. CAFs are a major component of the TME, and their interactions with tumor cells and other stromal elements contribute to various aspects of cancer biology, including tumor growth, metastasis, and resistance to therapy. Importantly, CAFs have been implicated in the pathogenesis of tumor cachexia through their ability to modulate inflammation, metabolic reprogramming, and immune responses. Given the intricate interplay between the TME, CAFs, and cachexia, understanding the mechanisms underlying these interactions is essential for developing effective therapeutic strategies to mitigate cachexia and improve patient outcomes. This review aims to provide a comprehensive overview of the roles of CAFs within the TME during cancer progression and the development of cachexia, highlighting the potential for targeting CAFs as a novel therapeutic approach.