Title:Metabolic Reprogramming of Cancer by Chemicals that Target Glutaminase Isoenzymes
Volume: 27
Issue: 32
关键词:
癌症代谢,组合治疗,谷氨酰胺酶同工酶,谷氨酰胺,谷氨酰胺酶抑制剂,代谢重编程。
摘要:
Background: Metabolic reprogramming of tumours is a hallmark of cancer. Among the
changes in the metabolic network of cancer cells, glutaminolysis is a key reaction altered in neoplasms.
Glutaminase proteins control the first step in glutamine metabolism and their expression
correlates with malignancy and growth rate of a great variety of cancers. The two types of glutaminase
isoenzymes, GLS and GLS2, differ in their expression patterns and functional roles: GLS
has oncogenic properties and GLS2 has been described as a tumour suppressor factor.
Results: We have focused on glutaminase connections with key oncogenes and tumour suppressor
genes. Targeting glutaminase isoenzymes includes different strategies aimed at deactivating the
rewiring of cancer metabolism. In addition, we found a long list of metabolic enzymes, transcription
factors and signalling pathways dealing with glutaminase. On the other hand, a number of chemicals
have been described as isoenzyme-specific inhibitors of GLS and/or GLS2 isoforms. These molecules
are being characterized as synergic and therapeutic agents in many types of tumours.
Conclusion: This review states the metabolic pathways that are rewired in cancer, the roles of glutaminase
isoforms in cancer, as well as the metabolic circuits regulated by glutaminases. We also
show the plethora of anticancer drugs that specifically inhibit glutaminase isoenzymes for treating
several sets of cancer.