Massachusetts General Hospital Cancer Center, Boston, 02114, USA.
Ann Intern Med. 2010 Nov 2;153(9):587-91. doi: 10.7326/0003-4819-153-9-201011020-00008.
Patients with metastatic melanoma have a poor prognosis and limited treatment options. In about one half of analyzed patients with metastatic melanoma, a mutated signal transduction molecule has been identified: v-raf murine sarcoma viral oncogene homolog B1 (BRAF). This molecule is part of an intracellular signaling cascade and may play a role in many different types of cancer. This article provides an overview of the current treatment options for metastatic melanoma and describes the pathophysiology underlying the development of therapies based on inhibition of BRAF. It summarizes findings of phase 1 and phase 2 studies of BRAF inhibitor therapy primarily in patients with metastatic melanoma, who have shown objective response rates of 70% to 80%. However, initial responses have not been sustained, with a median time to relapse of approximately 9 months. Clinicians should be aware of phase 3 trials of these agents and trials combining these therapies with other novel therapies because, at a minimum, BRAF inhibitors seem to be valuable as palliative therapy for metastatic melanoma.
转移性黑色素瘤患者预后较差，治疗选择有限。在分析的大约一半转移性黑色素瘤患者中，已经确定了一个突变的信号转导分子：v-raf 鼠肉瘤病毒致癌基因同源物 B1（BRAF）。该分子是细胞内信号级联的一部分，可能在许多不同类型的癌症中发挥作用。本文概述了转移性黑色素瘤的当前治疗选择，并描述了基于 BRAF 抑制的治疗方法发展的病理生理学基础。它总结了主要针对转移性黑色素瘤患者的 BRAF 抑制剂治疗的 1 期和 2 期研究结果，这些患者的客观缓解率为 70%至 80%。然而，初始反应并未持续，大约 9 个月就会复发。临床医生应该了解这些药物的 3 期试验以及将这些治疗方法与其他新型治疗方法联合应用的试验，因为至少 BRAF 抑制剂作为转移性黑色素瘤的姑息治疗似乎具有价值。
