Targeting methionine metabolism in cancer: opportunities and challenges.

Tumor cells depend on methionine because of higher methionine cycle flux and cellular methylation level, as well as impaired endogenous methionine biosynthesis. Tumorigenesis drives methionine metabolism for methylation for immune evasion. There are several methioninases and metabolic inhibitors under development as innovative therapeutics targeting tumor methionine metabolism. Reprogramming of methionine metabolism is a conserved hallmark of tumorigenesis. Recent studies have revealed mechanisms regulating methionine metabolism within the tumor microenvironment (TME) that drive both cancer development and antitumor immunity evasion. In this review article we summarize advancements in our understanding of tumor regulation of methionine metabolism and therapies in development that target tumor methionine metabolism. We also delineate the challenges of methionine blockade therapies in cancer and discuss emerging strategies to address them. [ABSTRACT FROM AUTHOR]