Short-chain fatty acids in the tumor microenvironment: from molecular mechanisms to cancer therapy

Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, serve as pivotal metabolites within the tumor microenvironment (TME), playing essential roles in modulating tumor progression. Although the biological functions and mechanisms of SCFAs in the TME show some overlap, each SCFA also exerts some distinct regulatory effects on tumors and TME. Notably, even a single SCFA may exhibit pleiotropic effects across different cancer types or under varying conditions within the same malignancy. Consequently, according to the different metabolic microenvironment of patients, precise modulation of SCFA levels could effectively suppress tumor progression. Furthermore, SCFAs have been shown to potentiate the therapeutic efficacy of immunotherapy, radiotherapy, and chemotherapy. This review systematically outlines the sources, biological functions, and mechanisms of different SCFAs in the TME, while exploring potential therapeutic strategies based on SCFA modulation. These insights offer novel perspectives and directions for future research and clinical cancer therapy.