Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation

Glutamine, the most abundant amino acid in human serum, serves not only as a key nutrient for maintaining normal cellular biological functions but also as an essential metabolic substrate for the proliferation and survival of tumor cells. Tumor cells exhibit a pronounced characteristic of “glutamine addiction” through metabolic reprogramming. This trait endows tumor cells with the dual capacity to exhibit both adaptability and vulnerability when confronted with regulated cell death (RCD) under metabolic stress, thereby opening up potential avenues for cancer therapy. This paper systematically reviews the biological functions of glutamine metabolism, delves into its relationships with various types of regulated cell death, elucidates its role in immune microenvironment, and summarizes the current application progress of anti-tumor drugs targeting glutamine metabolism.