Raf激酶抑制剂及其耐药机制研究进展

Advances in the Research of Raf Kinase Inhibitors and Drug Resistance Mechanisms

Ras/Raf/MEK/ERK通路是调节细胞生长与增殖的重要信号传导通路。在Ras/Raf/MEK/ERK通路中某些成员的突变往往与恶性肿瘤的发生密切相关。B-Raf激酶是该通路中Raf家族最重要的亚型,其主要突变形式B-Raf^(V600E)在黑色素瘤等多种肿瘤中高度表达。选择性B-Raf^(V600E)抑制剂vemurafenib和dabrafenib的上市使得晚期黑色素瘤的治疗进入新纪元,但是耐药性和副作用依然限制了二者的使用。综述目前Raf激酶抑制剂耐药性与副作用产生机制以及Raf激酶抑制剂的最新研究进展。

Ras/Raf/MEK/ERK signal transduction pathway plays significant roles in regulating a variety of cellular processes.Mutations of some key components in this pathway have been found to be closely related to the development of several malignancies.B-Raf kinase is the most important subtype of Raf family and its B-Raf^（V600E） mutant is highly expressed in many types of cancer including melanoma.The licensing of selective B-Raf kinase inhibitors,vemurafenib and dabrafenib,started a new era for the treatment of advanced B-Raf^（V600E）-mutant melanoma.However,drug resistance and side effects still exist.This paper reviewed most recent advances in the research of Raf kinase inhibitors as well as the mechanism of drug resistance and side effects.