Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.

Metabolic reprogramming is a hallmark of tumor initiation and progression. Previous studies have focused mainly on glucose and lipid metabolism, with emphasis on the Warburg effect and de novo lipogenesis. Based on the shift in research paradigms, this review focuses on amino acid metabolism, which has long been overlooked, and systematically elaborates how tumors hijack amino acid pathways to construct an immunosuppressive and protumor microenvironment. We confirm that amino acid metabolism acts as a core driver of tumor proliferation, immune evasion and therapeutic resistance. This paper further discusses the intricate regulatory crosstalk between amino acid metabolism and convent ional antitumor therapies, clarifying the potential of metabolic-targeted strategies in overcoming drug resistance and improving clinical efficacy. Deviating from the traditional perception that amino acids merely serve as auxiliary substances for glucose and lipid metabolism, we summarize their vital roles in remodeling the immunosuppressive tumor microenvironment and provide theoretical support for the clinical integration of precise metabolic targeted therapy and existing antitumor regimens combined with cutting-edge technologies.