Bahrami Afsane, Hesari AmirReza, Khazaei Majid, Hassanian Seyed Mahdi, Ferns Gordon A, Avan Amir
Department of Modern Sciences and Technologies, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
J Cell Physiol. 2018 Mar;233(3):2162-2169. doi: 10.1002/jcp.25952. Epub 2017 May 23.
Colorectal cancer is among the most lethal malignancies globally. BRAF is a member of the RAS/RAF/MEK/ERK signaling pathway. Its constitutive activation can result in increased cellular growth, development, invasion, and resistance to therapy. A mutation of the BRAF gene is present in 5-10% of metastatic colorectal cancers. BRAF mutations have been found to predict a lack of benefit to anti-EGFR therapy in metastatic CRC. Furthermore, CRC containing the BRAF V600E mutation display an innate resistance to BRAF inhibitors. The mechanisms of cell resistance can be explained at least in part by ERK dependent and ERK in-dependent pathway. Clinical trials evaluating the combinations of BRAF, PI3K, EGFR, and/or MEK inhibitors have revealed promising activity in BRAF mutant containing CRCs. There may be some benefit from future studies that focus on improving the efficacy of combined therapy in CRC with respect to the sustained effects. The aim of current review is to give an overview about the current status and prospective regarding the therapeutic potential of targeting BRAF mutant colorectal cancer.
结直肠癌是全球最致命的恶性肿瘤之一。BRAF是RAS/RAF/MEK/ERK信号通路的成员。其组成性激活可导致细胞生长、发育、侵袭增加以及对治疗产生抗性。BRAF基因的突变存在于5%-10%的转移性结直肠癌中。已发现BRAF突变预示着转移性结直肠癌患者接受抗表皮生长因子受体（EGFR）治疗无效。此外，含有BRAF V600E突变的结直肠癌对BRAF抑制剂表现出固有抗性。细胞抗性机制至少部分可由ERK依赖性和非ERK依赖性途径解释。评估BRAF、PI3K、EGFR和/或MEK抑制剂联合使用的临床试验已显示出在含有BRAF突变的结直肠癌中有良好活性。未来专注于提高联合治疗在结直肠癌中持续疗效的研究可能会带来一些益处。本综述的目的是概述靶向BRAF突变型结直肠癌治疗潜力的现状和前景。
