Targeting lipid metabolism in CAFs: A therapeutic opportunity in solid tumors

Cancer-associated fibroblasts (CAFs), representing the predominant stromal cell population within the solid tumor microenvironment (TME), are thought to play a significant role in facilitating tumorigenesis and progression. Nonetheless, recent experimental efforts to eradicate CAFs in solid tumors have inadvertently resulted in tumor progression, potentially due to the tumor-suppressive effects exhibited by specific CAF subtypes. Therefore, strategies that selectively target pro-tumorigenic CAFs may yield more favorable outcomes. Emerging evidence indicates that CAFs are instrumental in reprogramming lipid metabolism within TME, fostering a high-fat, immunosuppressive environment. To adapt to the hypoxic and nutrient-limited conditions of TME, cancer cells alter their metabolic processes, which subsequently influences the behavior of CAFs. The variability among CAF populations affects the metabolic pathways of cancer cells and neighboring immune cells. Despite the importance of these interactions, the discussion regarding lipid metabolism crosstalk between CAFs and the TME remains insufficiently explored in the literature. As a result, this study systematically reviews the various origins and heterogeneity of CAFs and closely investigates their roles in lipid metabolism reprogramming within the TME. Additionally, we analyze the metabolic interactions between CAFs and different components of the TME in solid tumors. Ultimately, we discuss potential therapeutic strategies and the challenges of targeting CAF lipid metabolism.