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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 pathway is an important signal transduction pathway regulating cell growth and proliferation. Mutations in some members of the Ras / Raf / MEK / ERK pathway are often closely related to the occurrence of malignant tumors. B-Raf kinase is the most important subtype of Raf family in this pathway. Its main mutant B-Raf ~ (V600E) is highly expressed in many tumors such as melanoma. The availability of selective B-Raf ~ (V600E) inhibitors, vemurafenib and dabrafenib, has brought a new era in the treatment of advanced melanoma, but drug resistance and side effects still limit the use of both. The current Raf kinase inhibitor drug resistance and side effects mechanism and Raf kinase inhibitors of the latest research progress.