靶向人滋养层细胞表面糖蛋白抗原2的抗肿瘤药物研究进展  

Research progress of anti-tumor drugs targeting trophoblast cell surface antigen 2

作　　者：鲍莹 樊彩云[1] 唐显[1] BAO Ying;FAN Caiyun;TANG Xian(Department of Nuclear Technology and Application,China Institute of Atomic Energy,Beijing102413,China)

机构地区：[1]中国原子能科学研究院核技术综合研究所,北京102413

出　　处：《中华肿瘤防治杂志》2024年第18期1154-1162,共9页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的探讨人滋养层细胞表面糖蛋白抗原2(Trop 2)结构与其在肿瘤增殖、迁移、侵袭和转移有关的信号通路中的功能,以及靶向Trop 2的抗肿瘤药物研究进展。方法以“人滋养层细胞表面糖蛋白抗原2、靶向治疗、肿瘤、抗体偶联药物、放射免疫治疗”为中文关键词,以“Trop 2、targeted therapy、tumors、antibody-drug conjugates、radioimmunotherapy”为英文关键词,检索中国知网、PubMed数据库1997-2023年发表的相关文献,纳入标准:(1)Trop 2结构及功能;(2)靶向Trop 2的抗体偶联类药物;(3)放射性标记靶向Trop 2的药物;(4)靶向Trop 2的光免疫疗法。排除标准:(1)与肿瘤相关性差;(2)无法得到全文;(3)临床前抗体偶联类药物(ADCs)的相关文献。最终纳入65篇文献。结果Trop 2是一种跨膜蛋白,不仅可以作为多种癌症的预测因子,通过各种信号通路控制细胞生长和扩散,还在多种实体瘤肿瘤细胞表面高表达,在正常组织中的表达极低。靶向Trop 2的ADCs主要有Sacituzumab govitecan、Datopotamab、deruxtecan(DS-1062)、SKB-264、DAC-002(JS-108)、ESG-401、FDA018、BAT-8003、RN927C(PF-06664178),主要用于治疗晚期或转移性三阴性乳腺癌,泌尿道上皮癌、非小细胞肺癌,乳腺癌、胃癌、小细胞肺癌和胰腺癌等实体肿瘤。靶向Trop 2的非ADCs主要包括(Rap)2-E1-(Rap)2、放射性标记药物和光免疫疗法等。Trop 2已成为精准医学的新靶点,如放射性核素、毒素和特异性抗体偶联结合成的药物等。结论靶向Trop 2的抗肿瘤药物研究在ADCs、放射性药物、光免疫疗法等方面取得了一定进展,目前多种药物已获批上市或处于临床试验阶段。同时,靶向Trop 2的药物联合治疗展现出良好的研究前景。Objective To investigate the structure of trophoblast cell surface antigen 2(Trop 2)and its signaling pathways involved in tumor proliferation,migration,invasion and metastasis,and the development of anti-tumor drugs targeting Trop 2.Methods The key words such as"Trop 2,targeted therapy,tumors,antibody-drug conjugates,radioimmunotherapy"were retrieved in CNKI,PubMed databases,mainly focusing on the related literature from 1997to 2023.The criteria for selection were:(1)The structure and function of Trop 2;(2)Antibody-drug conjugates targeting Trop 2;(3)Radiolabeled drugs targeting Trop 2;(4)Photoimmunotherapy targeting Trop 2.The exclusion criteria were:(1)Poor correlation with tumor;(2)Unfull text;(3)Preclinical ADC drugs,and 65articles were included.Results Trop 2is a transmembrane protein that not only serves as a predictive factor for various types of cancer,controlling cell growth and diffusion through various signaling pathways,but also has high expression on the surface of various solid tumor cells and extremely low expression in normal tissues.ADCs targeting Trop 2mainly include Sacituzumab govitecan,Datopotamab,deruxtecan(DS-1062),SKB-264,DAC-002(JS-108),ESG-401,FDA018,BAT-8003and RN927C(PF-06664178),which are mainly used to treat advanced or metastatic triple negative breast cancer,upper urinary tract cancer,non small cell lung cancer,breast cancer,gastric cancer,small cell lung cancer,pancreatic cancer and other solid tumors.The non ADC drugs targeting Trop 2mainly include(Rap)2-E1-(Rap)2,radiopharmaceuticals,and photoimmunotherapy.Trop 2has become a new target for precision medicine,such as drugs synthesized by coupling radioactive isotopes,toxins,and specific antibodies.Conclusion The research on anti-tumor drugs targeting Trop 2has made some achievements in ADCs,radiopharmaceuticals,photoimmunotherapy.At present,several drugs have been approved for marketing or are in clinical trials.At the same time,the drug combination therapy targeting Trop 2shows a good research prospect.

关 键 词：人滋养层细胞表面糖蛋白抗原2 靶向治疗 肿瘤 抗体偶联药物 放射免疫治疗 

分 类 号：R73[医药卫生—肿瘤]