Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review)

Amino acid (AA) sensing plays an important role in maintaining cellular metabolic homeostasis as well as tumorigenesis and progression. Studies on classic AA sensing pathways such as rapamycin complex 1 (mTORC1) and general control nonderepressible 2 (GCN2) have revealed their central position in cancer metabolic reprogramming. AA sensing pathways are often hijacked in tumors to adapt to the nutrient‑deprived microenvironment, promoting cell proliferation, anti‑apoptosis and treatment tolerance. In addition, the regulation of AA sensing and transport plays a crucial role in maintaining the metabolic flexibility of tumor cells. By targeting the AA sensing mechanism, it is expected to disrupt the metabolic homeostasis of cancer cells, providing new strategies for precision therapy. The present review summarized the latest advances in the research on the role of the mTORC1 and GCN2 AA sensing pathways in tumor metabolism, emphasizing their potential and the challenges faced in cancer diagnosis and treatment. Additionally, it provided novel insights into the therapeutic targeting of AA sensing pathways and proposes future research directions aimed at overcoming current limitations in cancer metabolism therapy.