弥漫型胃癌的治疗探索  

Exploring therapeutic strategies for diffuse gastric cancer

作　　者：孙孟婷 王斌 Mengting Sun;Bin Wang(Department of Gastroenterology,Daping Hospital,Army Medical University(Third Military Medical University),Chongqing Key Laboratory of Digestive Malignancies,Chongqing 400042,China)

机构地区：[1]中国人民解放军陆军军医大学陆军特色医学中心(大坪医院)消化内科,重庆市消化系统肿瘤精准防治重点实验室,重庆市400042

出　　处：《中国肿瘤临床》2023年第6期302-308,共7页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金项目(编号:81822032、91959111);重庆市自然科学基金项目(编号:cstc2019jcyjjqX0027)资助。

摘　　要：弥漫型胃癌(diffuse gastric cancer,DGC)是一种分化程度低、恶性程度高、临床预后差的胃腺癌亚型,异质性强,可由CDH1基因突变、RHOA基因突变和CLDN18-ARHGAP基因融合等驱动,也存在广泛的环境-基因突变互作,发病机制尚不清楚。已有的DGC研究模型包括基因修饰小鼠、人源肿瘤异种移植(patient-derived tumor xenograft,PDX)模型以及类器官模型,有机整合这些研究模型有助于更加准确地探索DCG病理生理过程,揭示DGC发生机制。临床上尚缺乏高效的DGC治疗药物,近年来开发了MET抑制剂、ROS1抑制剂等多种分子靶向药物,但未获得显著的临床疗效。鉴于此,本文展望宏基因组学、蛋白组学、代谢组学等新兴领域,综合DGC时空异质性、胃癌微生态调控和多组学整合的分子分型等前沿成果,提出DGC精准治疗的未来着力点和攻关方向,以期为DGC精准诊疗提供理论参考。Diffuse gastric cancer(DGC)is a subtype of gastric adenocarcinoma with low differentiation,high malignancy,and a poor clinical prognosis.DGC is highly heterogeneous and can be driven by mutations in the CDH1,RHOA,and CLDN18-ARHGAP gene fusion and wide-ranging environmental gene mutation interactions.However,its pathogenesis is unclear.The existing DGC models include transgenic mice,patient-derived tumor xenograft(PDX),and organoid models.The organic integration of these models will aid in a more accurate investigation of the pathophysiological process and the mechanism of DCG.In clinical practice,there is a lack of effective drugs for DGC treatment.Although a few molecular-targeted drugs,such as MET and ROS1 inhibitors,have been developed recently,they have not demonstrated any significant clinical efficacy.Thus,in this paper,we look forward to emerging fields such as metagenomics,proteomics,and metabolomics,and explore cutting-edge perspectives such as spatiotemporal heterogeneity of DGC,gastric cancer microecological regulation,and molecular typing for multi-omics integration,to put forward the focus and direction of DGC precision therapy in future,which can provide theoret-ical reference for DGC precision diagnosis and treatment.

关 键 词：弥漫型胃癌 分子分型 精准医疗 

分 类 号：R735.2[医药卫生—肿瘤]