Affiliation
Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester M23 9LIssue Date
2021
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KRAS is one of the most common human oncogenes, but concerted efforts to produce direct inhibitors have largely failed, earning KRAS the title of "undruggable". Recent efforts to produce subtype specific inhibitors have been more successful, and several KRASG12C inhibitors have reached clinical trials, including adagrasib and sotorasib, which have shown early evidence of efficacy in patients. Lessons from other inhibitors of the RAS pathway suggest that the effect of these drugs will be limited in vivo by the development of drug resistance, and pre-clinical studies of G12C inhibitors have identified evidence of this. In this review we discuss the current evidence for G12C inhibitors, the mechanisms of resistance to G12C inhibitors and potential approaches to overcome them. We discuss possible targets of combination therapy, including SHP2, receptor tyrosine kinases, downstream effectors and PD1/PDL1, and review the ongoing clinical trials investigating these inhibitors.Citation
Dunnett-Kane V, Nicola P, Blackhall F, Lindsay C. Mechanisms of Resistance to KRAS(G12C) Inhibitors. Cancers (Basel). 2021;13(1).Journal
CancersDOI
10.3390/cancers13010151PubMed ID
33466360Additional Links
https://dx.doi.org/10.3390/cancers13010151Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.3390/cancers13010151
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