天津医药

天津医药 ›› 2022, Vol. 50 ›› Issue (2): 214-219.doi: 10.11958/20212135

• 综述 • 上一篇    下一篇

BRAF突变型黑色素瘤的耐药性机制及治疗最新研究进展 #br#

李细媛，朱智鑫，赵海龙
  

  1. 1遵义医科大学基础医学院病理生理学教研室（邮编563000）；2遵义医科大学附属医院医务处病案管理科
  • 收稿日期:2021-09-15 修回日期:2021-10-09 出版日期:2022-02-15 发布日期:2022-02-15
  • 通讯作者: 李细媛 E-mail:200644552@qq.com
  • 基金资助:
    国家自然科学基金资助项目（82060503）；贵州省科技计划项目（黔科合基础［2019］1334号）；贵州省卫健委科学技术基金项目 （gzwjkj2019-1-033）

Recent advances in the mechanisms of drug resistance and treatment of BRAF-mutant melanoma

LI Xiyuan, ZHU Zhixin, ZHAO Hailong #br#   

  1. 1 Department of Pathophysiology, School of Preclinical Medicine, Zunyi Medical University, Zunyi 563000, China; 2 Medical
    Department, the Affiliated Hospital of Zunyi Medical University
  • Received:2021-09-15 Revised:2021-10-09 Published:2022-02-15 Online:2022-02-15

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摘要： 黑色素瘤是发病率和病死率极高的皮肤原发恶性肿瘤，其中50%携带原癌基因鼠类肉瘤滤过性毒菌致癌 同源体B1（BRAF）突变。BRAF抑制剂和丝裂原活化的细胞外信号调节激酶（MEK）抑制剂联用是BRAF突变型黑色 素瘤的主要治疗方法，但已出现一定耐药性和药物不良反应。目前认为BRAF突变型黑色素瘤耐药性包括原发性耐 药、适应性耐药和继发性耐药，相应分子机制存在一定联系和区别。同时，为了减少BRAF突变型黑色素瘤耐药性发 生，已开展新靶点抑制剂、免疫疗法和表观遗传学方面的基础及临床应用方面的研究，并取得了一定进展。就BRAF 突变型黑色素瘤发生耐药性的可能机制、治疗方案优化的现状及前景进行总结。

关键词: 黑色素瘤, 抗药性, 肿瘤, 分子靶向治疗, 免疫疗法, 原癌基因蛋白质B-raf, 丝裂原激活蛋白激酶激酶类, 酶抑制剂, BRAF突变型

Abstract: Melanoma is the primary malignant tumor of the skin with a very high morbidity and fatality, of which 50% are caused by viral infection of proto-oncogene BRAF mutation. The combination of BRAF and MEK inhibitors is the main treatment of BRAF mutant melanoma, but there have been some drug resistance and drug side effects. Currently, resistance of BRAF mutant melanoma is considered to include primary resistance, adaptive resistance and secondary resistance, and corresponding molecular mechanisms are related and different. At the same time, in order to reduce the incidence of drug resistance in BRAF mutant melanoma, some progress has been made in basic research and clinical application of new target inhibitors, immunotherapy and epigenetics. In this paper, we will summarize the possible mechanism of drug resistance in BRAF mutant melanoma and the current situation and prospects of optimized treatments.

Key words: melanoma, drug resistance, neoplasm, molecular targeted therapy, immunotherapy, proto-oncogene proteins B-raf, mitogen-activated protein kinase kinases, enzyme inhibitors, BRAF mutation type