Conroy Michael, Cowzer Darren, Kolch Walter, Duffy Austin G
Department of Medical Oncology, Mater Misericordiae University Hospital, Dublin 7, Ireland.
Authors contributed equally.
Cancer Drug Resist. 2021 Apr 8;4(3):543-558. doi: 10.20517/cdr.2021.07. eCollection 2021.
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).
RAS致癌基因是人类癌症中最常见的突变致癌基因，RAS突变型癌症是人类疾病的主要负担。尽管这些致癌基因在几十年前就已被发现，但近年来在对其结构和功能的理解方面取得了重大进展，包括不同异构体的治疗和预后意义。尽管在抑制RAS效应信号传导方面取得了一些成功，但事实证明，针对这些突变具有挑战性。最近，在试验环境中实现了对RAS的直接抑制。虽然这尚未转化为日常临床实践，但这一进展很有前景。本综述总结了已采取的多种RAS抑制方法，然后重点介绍直接抑制KRAS(G12C)的最新进展。
