摘要
RAS oncogenes are the most commonly mutated oncogenes in human cancer,and RAS-mutant cancers represent a major burden of human disease.Though these oncogenes were discovered decades ago,recent years have seen major advances in understanding of their structure and function,including the therapeutic and prognostic significance of diverse isoforms.Targeting of these mutations has proven difficult,despite some successes with inhibition of RAS effector signalling.More recently,direct RAS inhibition has been achieved in a trial setting.While this has yet to be translated to everyday clinical practice,this development carries much promise.This review summarizes the diverse approaches that have been taken to RAS inhibition and then focuses on the most recent developments in direct inhibition of KRAS(G12C).
基金
Funding source:Work in Walter Kolch’s lab is funded by Science Foundation Ireland(SFI)under Grant Numbers 18/SPP/3522 and 14/IA/2395.
作者简介
Michael Conroy,Authors contributed equally;Darren Cowzer,Authors contributed equally;Correspondence to:Austin G.Duffy,Department of Medical Oncology,Mater Misericordiae University Hospital,Dublin 7,Ireland.E-mail:austinduffy@mater.ie。
