Targeting Asparagine Metabolism in Solid Tumors

Reprogramming of energy metabolism to support cellular growth is a "hallmark" of cancer, allowing cancer cells to balance the catabolic demands with the anabolic needs of producing the nucleotides, amino acids, and lipids necessary for tumor growth. Metabolic alterations, or "addiction", are promising therapeutic targets and the focus of many drug discovery programs. Asparagine metabolism has gained much attention in recent years as a novel target for cancer therapy. Asparagine is widely used in the production of other nutrients and plays an important role in cancer development. Nutritional inhibition therapy targeting asparagine has been used as an anticancer strategy and has shown success in the treatment of leukemia. However, in solid tumors, asparagine restriction alone does not provide ideal therapeutic efficacy. Tumor cells initiate reprogramming processes in response to asparagine deprivation. This review provides a comprehensive overview of asparagine metabolism in cancers. We highlight the physiological role of asparagine and current advances in improving survival and overcoming therapeutic resistance.