Methionine adenosyltransferase 2A (MAT2A) inhibitors as single agents or in combination strategy for cancer therapy

Methylthioadenosine phosphorylase (MTAP)-deletion occurs in about 15% of all cancers. The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was found to elicit synthetic lethality in MTAP-deleted cancers. Here, we commented on a novel MAT2A inhibitor SCR-7952, and discussed the potential of MAT2A inhibitors as single agents or in combination for cancer therapy, including solid tumors and hematologic malignancies. Several MAT2A inhibitors with high efficacy and selectivity have been discovered. And MAT2A inhibitors synergize strongly with protein arginine N-methyltransferase 5 (PRMT5) inhibitors, taxanes, platinum, topoisomerase inhibitors, and antibody-drug conjugates (ADC). A MAT2A inhibitor IDE397 and the combination strategies with chemotherapies or other targeted therapies are under investigation in clinical. The promising preliminary clinical results demonstrate the potential of MAT2A inhibitors for the treatment of MTAP-deleted tumors.