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黑色素瘤中激酶抑制剂的临床应用进展。

Update on the clinical use of kinase inhibitors in melanoma.

机构信息

Department of Dermatology, Venereology, and Allergology, University Medical Center Essen, University of Duisburg-Essen, Germany, and German Cancer Consortium (DKTK), Essen, Germany.

出版信息

J Dtsch Dermatol Ges. 2017 Sep;15(9):887-893. doi: 10.1111/ddg.13321.

Abstract

The identification of targetable molecules in cellular signaling pathways represents a milestone in the treatment of melanoma. Selective inhibitors of these molecules, known as phosphokinases, allow for individual signaling pathways to be "switched off". This is of particular importance for tumors in which these pathways are constitutively activated by mutations in genes encoding said molecules. Especially patients with BRAF-mutated melanomas significantly benefit from kinase inhibitor therapies, with the current standard of combined BRAF and MEK inhibition providing very good long-term disease control. Such regimens have been shown to achieve a progression-free survival of more than ten months and an overall survival of more than two years, along with good quality of life. Given that the majority of patients develop secondary resistance during long-term kinase inhibitor therapy, current clinical trials are geared towards finding suitable drug combinations including inhibitors of other signaling pathways as well as immune checkpoint inhibitors. The present review highlights targeted therapies for melanoma currently available as well as potential future options presently under clinical investigation.

摘要

在细胞信号通路中鉴定可靶向的分子是治疗黑色素瘤的一个里程碑。这些分子(已知的磷酸激酶)的选择性抑制剂可使单个信号通路“关闭”。对于这些通路由于编码这些分子的基因突变而持续激活的肿瘤,这一点尤其重要。特别是 BRAF 突变型黑色素瘤患者从激酶抑制剂治疗中显著获益,目前联合 BRAF 和 MEK 抑制的标准方案可提供非常好的长期疾病控制。这些方案已显示出超过十个月的无进展生存期和超过两年的总生存期,同时具有良好的生活质量。鉴于大多数患者在长期激酶抑制剂治疗期间会出现继发性耐药,目前的临床试验旨在寻找合适的药物组合,包括其他信号通路抑制剂以及免疫检查点抑制剂。本综述强调了目前可用于黑色素瘤的靶向治疗以及目前正在临床研究中的潜在未来选择。

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