Ras突变型晚期黑色素瘤治疗  

Advances in the Treatment of Advanced Melanoma with Ras Mutations

作　　者：向梅 赵东丽[1] 张喜凤[1] 张艳玲[1] 王艳[1] 胡姗姗[1] 毛玉焕 张维真[1] 梁宪斌[1] XIANG Mei;ZHAO Dongli;ZHANG Xifeng;ZHANG Yanling;WANG Yan;HU Shanshan;MAO Yuhuan;ZHANG Weizhen;LIANG Xianbin(Department of Medical Oncology,the Third People′s Hospitalof Zhengzhou,Zhengzhou 450000,China)

机构地区：[1]郑州市第三人民医院黑色素瘤肿瘤内科,河南郑州450000

出　　处：《皮肤科学通报》2025年第1期20-29,共10页Dermatology Bulletin

摘　　要：大鼠肉瘤(rat sarcoma,Ras)基因是实体肿瘤中最常见的原癌基因,由于突变亚型中缺乏药理学上可靶向的口袋,Ras历来被认为是不可成药的靶点。然而,药物设计的改进最终导致了对活性或非活性状态的突变鼠类肉瘤病毒癌基因(kirsten rat sarcoma viral oncogene,Kras)具有选择性的抑制剂的开发。其中一些抑制剂已被证明对Kras G12C/G12D突变癌症患者有效,并已成为实践的改变。癌细胞和肿瘤微环境中RAS信号传导的理解不断提高,逐渐探究出新的药物或联合治疗的潜力,目前正在临床试验中进行探索。本文阐述了Ras突变的作用机制及黑色素瘤中Ras突变的特点及近年来该领域的研究进展,旨在展示该突变患者的治疗现状,并对各种新型治疗方法的数据进行归纳和总结,为临床实践方案提供新的治疗思路。Although Ras is the most common oncogenic protein in solid tumors,it has historically been considered an undruggable target due to the lack of pharmacologically targetable pockets in its mutant subtypes.However,improvements in drug design have ultimately led to the development of selective inhibitors for mutant Kras in either its active or inactive states.Some of these inhibitors have proven efficacy in patients with Kras G12C/G12D-mutant cancers and have become practice changing.Our understanding of RAS signaling in cancer cells and the tumor microenvironment continues to improve,gradually uncovering the potential for new drugs or combination therapies,which are currently being explored in clinical trials.This review summarizes the mechanisms of Ras mutations,the characteristics of Ras mutations in melanoma,and research advancements in this field in recent.It aims to present the current treatment landscape for patients with these mutations and to summarize and analyze data on various novel treatment approaches,providing new treatment options for practice.

关 键 词：Ras突变 黑色素瘤 治疗 

分 类 号：R739.6[医药卫生—肿瘤] R751[医药卫生—临床医学]