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[黑色素瘤的靶向治疗]

[Targeted therapies for melanoma].

作者信息

Leiter U, Meier F, Garbe C

机构信息

Zentrum für Dermato-Onkologie, Universitäts-Hautklinik, Eberhard-Karls-Universität Tübingen, Liebermeisterstr. 25, 72076, Tübingen, Deutschland,

出版信息

Hautarzt. 2014 Jul;65(7):600-6. doi: 10.1007/s00105-013-2735-6.

Abstract

Since the discovery of activating mutations in the BRAF oncogene and also stimulation of immune mediated antitumor response in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. This article addresses the latest developments of BRAF/MEK/ERK pathway signaling. In addition, the development of drugs to attack alternative mutations in melanoma, such as NRAS and KIT is described. Strategies for the management of BRAF inhibitor resistance, such as with combination therapy, are outlined. Antitumor immune therapies with monoclonal antibodies such as ipilimumab which acts by promoting T-cell activation or antibody blockade of programmed death-1 (PD-1) led to a long term response in metastatic melanoma. Results of latest clinical studies including the toxicity profile are described. Due to selective kinase inhibitors and immune checkpoint blockade, the therapy of unresectable metastatic melanoma has greatly improved and long-term survival of patients with metastatic melanoma seems a real possibility.

摘要

自从发现BRAF癌基因中的激活突变以及黑色素瘤中免疫介导的抗肿瘤反应受到刺激以来,不可切除和转移性黑色素瘤的靶向治疗取得了显著进展。本文阐述了BRAF/MEK/ERK信号通路的最新进展。此外,还描述了针对黑色素瘤中其他替代突变(如NRAS和KIT)的药物研发情况。概述了应对BRAF抑制剂耐药性的策略,如联合治疗。使用单克隆抗体的抗肿瘤免疫疗法,如通过促进T细胞活化起作用的伊匹单抗或程序性死亡-1(PD-1)抗体阻断,在转移性黑色素瘤中产生了长期反应。描述了包括毒性特征在内的最新临床研究结果。由于选择性激酶抑制剂和免疫检查点阻断,不可切除转移性黑色素瘤的治疗有了很大改善,转移性黑色素瘤患者长期生存似乎成为现实。

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