HER-2基因突变在恶性实体瘤中的临床研究进展

Progress in clinical research of HER-2 gene mutation in malignant solid tumors

近年来,随着在分子水平上对肿瘤发生、发展研究的深入,人们对HER-2这一原癌基因在恶性实体瘤中的作用有了丰富的认识。有研究表明,与传统的HER-2基因扩增相比,某些HER-2“热点”突变在多种癌症类型中起致癌性驱动作用,且在体外和体内均具有转化能力,有临床试验也验证了以HER-2为靶点的药物对各种携带HER-2突变肿瘤的敏感性。此外,应用下一代测序(NGS)或实时定量PCR(RT-PCR)对活检组织或循环游离DNA(cfDNA)中的基因突变可进行鉴定。本文就HER-2突变在不同恶性实体瘤中的研究现状和临床进展情况进行综述,包括HER-2基因的基本结构与功能、检测方法、突变类型及治疗策略等,以便为下一代抗HER-2靶向治疗提供新的思路和指导。

In recent years,with the deepening of research on tumorigenesis and development at the molecular level,people have a rich understanding of the role of HER-2,a proto-oncogene,in malignant solid tumors.Recent studies have shown that certain HER-2"hot spot"mutations are carcinogenic in a variety of cancer types compared to traditional HER-2 gene amplification,and have transforming ability in vitro and in vivo.Recent clinical trials have also shown the sensitivity of HER-2-targeted drugs to tumors carrying various HER-2 mutations.In addition,gene mutations in biopsy tissue or circulating free DNA(cfDNA)can be identified using next-generation sequencing(NGS)or real-time quantitative PCR(RT-PCR).This article reviews the current status and clinical application of HER-2 mutations in different malignant solid tumors,including the basic structure and function of HER-2 gene,detection methods,mutation types,and treatment strategies,in order to provide ideas and guidance for the next generation of anti-HER-2 targeted therapies.