Department of Medicine, Division of Hematology/Oncology, University of California Los Angeles, and Jonsson Comprehensive Cancer Center at UCLA, 11-934 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
Nat Rev Clin Oncol. 2011 May 24;8(7):426-33. doi: 10.1038/nrclinonc.2011.69.
After decades of stagnation, recent therapeutic advances in melanoma seem on the horizon. The discovery of the genetic underpinnings of this historically refractory disease has exposed potential targets for therapy, BRAF mutations being principal among them. In the 8 years following the discovery of BRAF mutations in 50-60% of advanced melanomas, only recently have potent and selective inhibitors of this intracellular signaling molecule shown efficacy from early clinical testing. Vemurafenib (PLX4032) and GSK2118436, two orally available and well tolerated agents are on the verge of transforming the landscape of melanoma therapy based on the promising results of their respective phase I, II, and III trials.
经过几十年的停滞不前，黑色素瘤的最近治疗进展似乎即将出现。对这种历史上难治性疾病的遗传基础的发现为治疗提供了潜在的靶点，其中 BRAF 突变是主要的靶点之一。在发现 BRAF 突变存在于 50-60%的晚期黑色素瘤之后的 8 年里，只有最近才发现这种细胞内信号分子的有效且选择性抑制剂，在早期临床试验中显示出疗效。vemurafenib（PLX4032）和 GSK2118436 是两种口服且耐受性良好的药物，根据各自的 I 期、II 期和 III 期临床试验的结果，它们即将改变黑色素瘤治疗的格局。
