Northwell Health Cancer Institute and Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, New York, USA.
Anticancer Drugs. 2020 Jul;31(6):545-557. doi: 10.1097/CAD.0000000000000940.
B-type Raf kinase (BRAF) mutations occur in approximately 10% of patients with metastatic colorectal cancers (mCRC). Tumors harboring this mutation have a unique molecular profile and clinical phenotype. Response rate to systemic chemotherapy is poor and associated with shorter survival rate. Although BRAF inhibition dramatically changed treatment for melanoma patients, similar clinical responses were not observed in BRAF-mutant CRC, proposing a distinct mechanism of carcinogenesis. The aggressive biology of BRAF-mutated mCRC has underlined the importance of developing new therapeutic agents to improve outcomes in these patients. Despite numerous attempts, chemotherapy regimens are limited for this population. Reactivation of mitogen activated protein kinase pathway may explain the resistance to monotherapy, thus different combinations to target the pathway at different levels have been studied. This article will describe most suitable treatment options for CRC patients with BRAF mutation and discuss new emerging agents.
B 型 Raf 激酶（BRAF）突变发生在约 10%的转移性结直肠癌（mCRC）患者中。携带这种突变的肿瘤具有独特的分子谱和临床表型。对系统化疗的反应率差，且与生存率较短有关。尽管 BRAF 抑制显著改变了黑色素瘤患者的治疗方法，但在 BRAF 突变的 CRC 中并未观察到类似的临床反应，提示存在不同的致癌机制。BRAF 突变的 mCRC 的侵袭性生物学特性强调了开发新的治疗药物以改善这些患者预后的重要性。尽管进行了多次尝试，但针对该人群的化疗方案有限。丝裂原活化蛋白激酶途径的再激活可能解释了对单药治疗的耐药性，因此已研究了不同的组合以在不同水平上靶向该途径。本文将描述 BRAF 突变的 CRC 患者的最适合治疗选择，并讨论新出现的药物。
