BRAF 突变型晚期皮肤黑色素瘤的治疗

Treatment of BRAF-mutated advanced cutaneous melanoma.

作者信息

Trinh Van Anh, You Yan, Hwu Wen-Jen

机构信息

Pharmacy Clinical Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The Third Affiliated Hospital of Harbin Medical University, Harbin 150081, China.

出版信息

Chin Clin Oncol. 2014 Sep;3(3):28. doi: 10.3978/j.issn.2304-3865.2014.05.10.

DOI:10.3978/j.issn.2304-3865.2014.05.10

PMID:25841454

Abstract

The field of melanoma oncology has recently awakened with groundbreaking scientific advances and innovative therapeutic strategies. New groups of small-molecule kinase inhibitors targeting the aberrant mitogen-activated protein kinase (MAPK) pathway activation mediating tumor growth and survival have revolutionized the therapeutic approach to advanced melanoma. BRAF and MEK inhibitors are the first groups of agents that improved all clinical efficacy endpoints, including response rate, progression-free survival (PFS) and overall survival (OS), in patients with BRAF-mutated advanced melanoma when compared with standard chemotherapy in randomized phase III studies. However, despite the impressive clinical responses in patients with BRAF mutant advanced melanoma, duration of response to MAPK pathway-targeted therapy remains limited, implicating rapid emergence of drug resistance. Diverse strategies to overcome tumor resistance to MAPK inhibitors, the focus of today's translational and clinical research, will further improve the clinical outcome for patients with BRAF-mutated advanced melanoma in the near future.

摘要

黑色素瘤肿瘤学领域最近因突破性的科学进展和创新的治疗策略而重新焕发生机。针对介导肿瘤生长和存活的异常丝裂原活化蛋白激酶（MAPK）通路激活的新型小分子激酶抑制剂，彻底改变了晚期黑色素瘤的治疗方法。与随机III期研究中的标准化疗相比，BRAF和MEK抑制剂是首批在BRAF突变的晚期黑色素瘤患者中改善了所有临床疗效终点的药物，包括缓解率、无进展生存期（PFS）和总生存期（OS）。然而，尽管BRAF突变的晚期黑色素瘤患者有令人印象深刻的临床反应，但对MAPK通路靶向治疗的反应持续时间仍然有限，这意味着耐药性迅速出现。克服肿瘤对MAPK抑制剂耐药性的各种策略是当今转化和临床研究的重点，在不久的将来将进一步改善BRAF突变的晚期黑色素瘤患者的临床结局。