Innate and adaptive resistance mechanisms to arginine deprivation therapies in sarcoma and other cancers  

作　　者：Leonard C.Rogers Brian A.Van Tine 

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

出　　处：《Cancer Drug Resistance》2019年第3期516-526,共11页癌症耐药（英文）

基　　金：BAVT-reports a one year grant from Polaris,Inc.in 2014,unrelated;Basic Science Grant Funding from Pfizer,Tracon,and Merck;consulting fees from Epizyme,Lilly,CytRX,Janssen,Immune Design,Daiichi Sankyo,Bayer,Plexxicon and Adaptimmune;speaking fees from Caris,Janseen and Lilly;Travel support from Lilly;and is the overall principle investigator on(NCT03449901).

摘　　要：Many cancers lack functional expression of the enzyme argininosuccinate synthetase 1(ASS1)that is necessary for synthesis of L-arginine.These cancers must import arginine for survival and growth,and this reliance can be targeted by arginine-degrading extracellular enzymatic drugs,most commonly PEGylated arginine deiminase.These enzymes can become targets of the immune system,reducing their effectiveness,but PEGylation improves the in vivo stability.Arginine deprivation causes cell death in some cancers,but others gain resistance by expressing ASS1 after a starvation response is induced.Other resistance mechanisms are possible and explored,but these have not been observed specifically in response to arginine deprivation.Future studies,especially focusing on the mechanisms of ASS1 upregulation and metabolic adaptations,may yield insights into preventing or taking advantage of resistance adaptations to make arginine deprivation therapy more effective.

关 键 词：PEGylated arginine deiminase argininosuccinate synthetase 1 resistance metabolism ARGININE 

分 类 号：R73[医药卫生—肿瘤]