PHGDH as a mechanism for resistance in metabolically-driven cancers  

作　　者：Richa Rathore Charles R.Schutt Brian A.Van Tine 

机构地区：[1]Division of Medical Oncology,Washington University in St.Louis,St.Louis,MO 63110,USA [2]Siteman Cancer Center,St.Louis,MO 63110,USA

出　　处：《Cancer Drug Resistance》2020年第4期762-774,共13页癌症耐药（英文）

基　　金：The authors would like to thank Dawn Merkel’s Bad to the Bone Chili Cook Off,Kellsie’s Hope Foundation;the National Institute of Health(NIH)-National Cancer Institute(NCI)(R01-CA227115)for funding.

摘　　要：At the forefront of cancer research is the rapidly evolving understanding of metabolic reprogramming within cancer cells.The expeditious adaptation to metabolic inhibition allows cells to evolve and acquire resistance to targeted treatments,which makes therapeutic exploitation complex but achievable.3-phosphoglycerate dehydrogenase(PHGDH)is the rate-limiting enzyme of de novo serine biosynthesis and is highly expressed in a variety of cancers,including breast cancer,melanoma,and Ewing’s sarcoma.This review will investigate the role of PHGDH in normal biological processes,leading to the role of PHGDH in the progression of cancer.With an understanding of the molecular mechanisms by which PHGDH expression advances cancer growth,we will highlight the known mechanisms of resistance to cancer therapeutics facilitated by PHGDH biology and identify avenues for combatting PHGDH-driven resistance with inhibitors of PHGDH to allow for the development of effective metabolic therapies.

关 键 词：PHGDH CANCER METABOLISM SERINE one-carbon metabolism folate cycle drug resistance 

分 类 号：R73[医药卫生—肿瘤]