Rose A A N
Department of Medicine, Division of Medical Oncology, University of Toronto, Toronto, Ontario, Canada.
Drugs Today (Barc). 2019 Apr;55(4):247-264. doi: 10.1358/dot.2019.55.4.2958476.
BRAF is a constituent of the mitogen-activated protein kinase (MAPK) signaling pathway, which serves to activate downstream MEK, and is one of the most commonly mutated oncogenes in human tumors. Indeed, BRAF V600 mutations are present in approximately 40% of metastatic melanoma tumors. Encorafenib (LGX-818, Braftovi) and binimetinib (MEK-162, Mektovi) are small-molecule inhibitors of BRAF and MEK, respectively. BRAF and MEK inhibitors have been shown to improve overall and progression-free survival among patients with metastatic melanoma. Of these inhibitors, encorafenib and binimetinib are the newest combination, which received approval by the Food and Drug Administration (FDA) for the treatment of BRAF V600E/K-mutated melanoma in June 2018. This review will focus on the preclinical pharmacology, pharmacokinetics and clinical utility of encorafenib and binimetinib in BRAF V600-mutated melanoma.
BRAF是丝裂原活化蛋白激酶（MAPK）信号通路的一个组成部分，该信号通路用于激活下游的MEK，并且是人类肿瘤中最常发生突变的致癌基因之一。事实上，BRAF V600突变存在于约40%的转移性黑色素瘤肿瘤中。恩考芬尼（LGX-818，Braftovi）和比美替尼（MEK-162，Mektovi）分别是BRAF和MEK的小分子抑制剂。BRAF和MEK抑制剂已被证明可改善转移性黑色素瘤患者的总生存期和无进展生存期。在这些抑制剂中，恩考芬尼和比美替尼是最新的组合，于2018年6月获得美国食品药品监督管理局（FDA）批准用于治疗BRAF V600E/K突变的黑色素瘤。本综述将聚焦于恩考芬尼和比美替尼在BRAF V600突变黑色素瘤中的临床前药理学、药代动力学及临床应用。
