BRAF突变在肿瘤克隆演化中的作用及研究进展  

Research progress on the role of BRAF mutations in the evolution of tumor clones

作　　者：王潇艳 龚飏 国风 WANG Xiaoyan;GONG Yang;GUO Feng(Department of Oncology,The Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou 215001,China)

机构地区：[1]南京医科大学附属苏州医院、苏州市立医院肿瘤内科,江苏苏州215001

出　　处：《临床肿瘤学杂志》2023年第8期760-765,共6页Chinese Clinical Oncology

基　　金：江苏省卫健委医学科研面上项目(M2020043)。

摘　　要：V-raf鼠肉瘤病毒癌基因同源体B(BRAF)编码丝裂原激活蛋白激酶信号通路上的丝氨酸-苏氨酸蛋白激酶,并参与着细胞的生长、增殖和分化。BRAF基因突变可以持续激活细胞外调节蛋白激酶,同肿瘤的发生发展相关。在内外环境的影响下,单克隆起源的肿瘤细胞中有增殖优势的细胞存活,而劣势细胞被淘汰,即肿瘤克隆演化。肿瘤的克隆演化常常与肿瘤细胞的异质性、恶性程度增高和耐药相关,其机制涉及肿瘤细胞、肿瘤微环境及局部免疫细胞的进化。针对BRAF突变型肿瘤克隆演化后的治疗仍无标准方案,目前探索性研究主要涉及相关通路的靶向抑制、异常蛋白和氨基酸的抑制及促进肿瘤细胞死亡。本文就BRAF突变型肿瘤的临床表型、演化机制及对肿瘤进化后的治疗性研究进行综述。V-raf murine sarcoma viral oncogene homolog(BRAF)encodes a serine-threonine protein kinase in the mitogen-activated protein kinases signaling pathway,which drives cellular growth,proliferation and differentiation.BRAF gene mutations consistently activate extracellular regulated protein kinases and promote tumor growth and survival.Under the influence of the internal and external environment,tumor cells with proliferative advantages survive,while disadvantaged cells are eliminated,i.e.,the clonal evolution of the tumor.Clonal evolution of tumors is often related to the development of tumor heterogeneity,increased degree of malignancy and the formation of drug resistance.Relevant mechanisms involve the evolution of tumor cells,the tumor microenvironment and local immune cells.However,the standard treatment for BRAF mutant tumors after clonal evolution has not yet been clarified,and present exploratory studies are mainly focused on targeting relevant signal pathways,protein inhibition and promotion of tumor cell death.This review summarizes the clinical phenotypes,evolutionary mechanisms and therapeutic research of BRAF mutant tumors after tumor evolution.

关 键 词：BRAF突变 克隆演化 信号通路 靶向治疗 耐药 

分 类 号：R73[医药卫生—肿瘤]