Carboxylic acid metabolism in cancer: Mechanisms, microenvironment interactions, and therapeutic opportunities

Cancer cells reprogram their metabolism to favor aerobic glycolysis and enhance carboxylic acid metabolism, supporting their energy needs and promoting tumor progression. This review explores the role of carboxylic acids, such as lactate, fatty acids, and amino acids, in cancer through four key pathways: (1) lactate-mediated tumor microenvironment acidification and immune suppression, (2) fatty acid metabolism driving tumorigenesis, (3) amino acid regulation of cancer cell survival, and (4) the crosstalk between these metabolic networks. These pathways contribute to immune evasion, proliferation, and drug resistance by modulating key enzymes, transporters, and signaling mechanisms. Despite their therapeutic potential, targeting carboxylic acid metabolism remains challenging owing to tumor adaptability and metabolic heterogeneity. Future research directions include the development of isoform-specific inhibitors, combination therapies, and precision medicine approaches based on metabolic profiling. Understanding these interconnected pathways may reveal new vulnerabilities for innovative cancer treatments.