{"title":"KRAS Q61H Mutation Confers Cancer Cells with Acquired Resistance to SHP2 Inhibition","authors":"Yi-Hui Song, Xin-yu Yang, Bin Yu","doi":"10.1055/s-0042-1743411","DOIUrl":null,"url":null,"abstract":"Cancer cells with varied KRAS mutations exhibit different sensitivity to SHP2 inhibition. A recent work published in Nature Communications revealed the underlying drug resistance mechanism of cancer cells harboring KRAS Q61H mutation to SHP2 inhibitors (SHP2i). 1 This work showed that KRAS Q61H mutation renders cancer cells resistant to SHP2i via decoupling KRAS from SHP2-mediated upstream nucleotide exchange factors for (guanine nucleotide exchange factor [GEF])/GTPase activating protein (GAP) regulation, providing newinsightsintotreatingcancerswithKRASQ61Hmutations. KRAS, the most frequently mutated RASisoform, isa proto-oncogene that encodes small GTPase transductor protein. In response to upstream signals, KRAS can switch between inactive guanosine diphosphate (GDP) state and active guano-sinetriphosphate (GTP) stateby GEFs, such as Sonof Sevenless (SOS),orGAPs. 2 KRASmutations,primarilyatcodons12,13,or 61, account for 86% of RAS mutations. In particular, glutamine","PeriodicalId":19767,"journal":{"name":"Pharmaceutical Fronts","volume":"13 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2022-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Fronts","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1055/s-0042-1743411","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1
Abstract
Cancer cells with varied KRAS mutations exhibit different sensitivity to SHP2 inhibition. A recent work published in Nature Communications revealed the underlying drug resistance mechanism of cancer cells harboring KRAS Q61H mutation to SHP2 inhibitors (SHP2i). 1 This work showed that KRAS Q61H mutation renders cancer cells resistant to SHP2i via decoupling KRAS from SHP2-mediated upstream nucleotide exchange factors for (guanine nucleotide exchange factor [GEF])/GTPase activating protein (GAP) regulation, providing newinsightsintotreatingcancerswithKRASQ61Hmutations. KRAS, the most frequently mutated RASisoform, isa proto-oncogene that encodes small GTPase transductor protein. In response to upstream signals, KRAS can switch between inactive guanosine diphosphate (GDP) state and active guano-sinetriphosphate (GTP) stateby GEFs, such as Sonof Sevenless (SOS),orGAPs. 2 KRASmutations,primarilyatcodons12,13,or 61, account for 86% of RAS mutations. In particular, glutamine