黏膜黑色素瘤的探索与治疗策略

盛锡楠; 鄢谢桥; 连斌; 崔传亮; 斯璐; 迟志宏; 孔燕; 郭军

doi:10.3969/j.issn.1000-8179.2021.07.363

黏膜黑色素瘤的探索与治疗策略

doi: 10.3969/j.issn.1000-8179.2021.07.363

北京大学肿瘤医院暨北京市肿瘤防治研究所肾癌黑色素瘤内科，恶性肿瘤发病机制及转化研究教育部重点实验室（北京市100142）

基金项目:

北京市医院管理局登封人才计划 DFL20181101

详细信息

作者简介:
盛锡楠专业方向为黑色素瘤及泌尿系统肿瘤的诊治。E-mail：doctor_sheng@126.com

郭军教授，主任医师，博士研究生导师。现任北京大学肿瘤医院副院长、肾癌黑色素瘤内科主任，兼任中国临床肿瘤协会（CSCO）理事长，CSCO黑色素瘤专家委员会主任委员，CS-CO肾癌专家委员会副主任委员，CSCO免疫治疗专家委员会副主任委员，国际黑色素瘤研究联盟亚太地区主席，全球黑色素瘤专家委员会常务委员，主要研究方向为黑色素瘤及泌尿系统肿瘤的精准治疗，牵头《CSCO黑色素瘤诊治指南》《CSCO肾癌诊治指南》及《CSCO尿路上皮癌诊治指南》的制订与推广。共发表SCI论著100余篇，累积影响因子近500分

通讯作者:
郭军 guoj307@126.com

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出版历程
- 收稿日期: 2021-10-27
- 刊出日期: 2021-04-15

Exploration and treatment strategy of mucosal melanoma

Department of Renal Cancer and Melanoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing 100142, China

Funds:

Beijing Municipal Administration of Hospitals' Ascent Plan DFL20181101

More Information

Corresponding author: Jun Guo; E-mail: guoj307@126.com

摘要

摘要: 黏膜黑色素瘤是黑色素瘤的一种罕见亚型，具有独特的生物学和临床特征。研究其特有的低突变负荷、高结构变异负荷和独特的驱动基因将有助于了解其自然病程及其对各种治疗的反应。目前仍缺乏黏膜黑色素瘤最佳治疗策略的共识。新的靶向治疗和免疫治疗的联合治疗是目前临床试验研究的方向。血管内皮生长因子（vascular endothelial growth factor，VEGF）被认为与不良预后相关，阻断该途径可以控制黑色素瘤的进展。此外，该途径在肿瘤微环境中还具有免疫抑制作用，体内研究显示同时抑制VEGF受体和细胞程序性死亡受体-1（programmed cell death-1，PD-1）途径，可以协同增强T细胞浸润，抑制肿瘤生长。PD-1单抗和VEGF受体抑制剂联合方案在晚期初治黏膜黑色素瘤中显示出良好的安全性和持久的抗肿瘤效果。总体而言，尽管其他亚型晚期黑色素瘤的全身治疗取得了巨大的进步，但黏膜黑色素瘤患者的预后仍不佳，这一罕见亚型的实验室和临床研究工作更为迫切地需要受到重视。
- 黏膜黑色素瘤 /
- 分子生物学 /
- 靶向治疗 /
- 免疫治疗
Abstract: Mucosal melanoma is a rare melanoma subtype with distinct biological, clinical, and management considerations. Its characteristically low mutational burden, high copy number and structural variants, and prevalence of unique driver mutation are important for understanding the natural history of mucosal melanoma and its response to various treatments. Knowledge regarding optimal treatment strategies for mucosal melanoma is limited. Thus, clinical trials, particularly those using a combination of newer targeted therapies and immunotherapies, are investigating novel treatment approaches. The expression of vascular endothelial growth factor (VEGF) is considered to be associated with poor outcomes in patients with mucosal melanoma, blocking VEGF signaling may control the growth of melanoma lesions. Besides its role in vascular growth, VEGF has emerged as an important immunosuppressive agent in the tumor microenvironment. In vivo studies have shown that angiogenesis inhibition, specifically the simultaneous inhibition of the VEGF receptor and PD-1 pathways, synergistically increased T-cell infiltration and suppressed tumor growth. The treatment combination of PD-1 blockade and a small-molecule VEGF receptor inhibitor for patients with previously untreated advanced mucosal melanoma demonstrated a manageable safety profile and durable antitumor activity. Overall, despite considerable therapeutic advances in the treatment of melanoma, the poor prognosis of patients with mucosal melanoma mandates continued emphasis on laboratory and clinical research for this rare melanoma subtype.
- mucosal melanoma /
- molecular biology /
- targeted therapy /
- immunotherapy

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