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摘要:
滋养层细胞表面抗原2（Trop2）是一种在正常组织中几乎不表达而在恶性实体肿瘤中高度表达的糖蛋白，且与其不良预后显著相关。目前，临床开发了多种针对Trop2的靶向疗法，例如抗Trop2抗体和靶向Trop2的抗体偶联药物（ADC），一些已经被批准或正在临床试验中用于癌症治疗。本文对Trop2的基因结构、作用机制及其在实体肿瘤中的临床研究和药物研发等方面进行阐述，为临床开发更加安全有效的针对Trop2的靶向药物提供参考。
Abstract:Trophoblast cell surface antigen 2 (Trop2) is a glycoprotein that is barely expressed in normal tissues but highly expressed in malignant tumors; it is remarkably associated with poor prognosis. Various targeted therapeutics against Trop2, such as anti-Trop2 antibodies and antibody-drug conjugate drugs targeting Trop2, have been developed, and some therapeutics have been approved or are in clinical trials for cancer treatment. In this review, we comprehensively discuss the gene structure, mechanism of action, clinical research, drug development, and other aspects of Trop2 to provide references for the clinical development of effective and safe Trop2-targeting drugs.
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Key words:
- Trop2 /
- Cancer /
- Mechanism /
- Structure /
- Targeted therapy
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Competing interests: The authors declare that they have no competing interests.利益冲突声明：所有作者均声明不存在利益冲突。作者贡献：张 颖：撰写初稿、文献检索和数据分析刘月平：文章整体思路设计和审阅
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图 1 使用公共数据库分析Trop2在肿瘤组织和正常组织中的表达情况
Figure 1 Expression of Trop2 in tumor and normal tissues analyzed using a public database
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图 2 Trop2在细胞中的定位（HPA数据库）
Figure 2 Trop2 localization in cells (HPA data source database)
表 1 靶向Trop2的ADC药物戈沙妥珠单抗在不同肿瘤中的临床疗效
Table 1 Clinical efficacy of ADC drug sacituzumab govitecan targeting Trop2 in different tumors
Tumor Drug Phase ORR Trial TNBC SG Ⅰ/Ⅱ ORR: 33.3% (n=108); mPFS: 5.5 m; mOS: 13.0 m NCT01631552 HR+/HER2-TNBC SG Ⅰ/Ⅱ ORR: 31.5% (n=54); mPFS: 5.5 m; mOS: 12 m NCT01631552 TNBC SG Ⅲ ORR: 35% (n=235); mPFS: 5.6 m; mOS: 12.1 m; NCT02574455 (2021) HR+/HER2- TNBC SG Ⅲ ORR: 21% (n=272); mPFS: 5.5 m; mOS: 14.4 m; NCT03901339 TNBC SG Ⅱ ORR: 64% (n=50); pCR: 30%; NCT04230109 UC SG Ⅰ ORR: 33% (n=25); mPFS: 6.7 m-8.2 m;
mOS: 7.5 m-11.4 mNCT01631552 UC SG Ⅱ ORR: 27% (n=113); mPFS: 5.4 m; mOS: 5.4 m NCT03547973 (Cohort 1) UC SG Ⅱ ORR: 32% (n=38); mPFS: 5.6 m; mOS: 13.5 m NCT03547973 (Cohort 2) UC SG + pembrolizumab Ⅱ ORR: 41% (n=17); mPFS: 5.3 m; mOS: 12.7 m NCT03547973 (Cohort 3) UC SG + ipilimumab +
nivolumabⅠ ORR: 41% (n=9); mPFS: 8.8 m NCT04863885 NSCLC SG Ⅰ ORR: 19% (n=47); mPFS: 5.2 m; mOS: 9.5 m NCT01631552 SCLC SG Ⅱ ORR: 14% (n=47); mPFS: 3.7 m; mOS: 7.5 m NCT01631552 CRC SG Ⅰ/Ⅱ ORR: 3.2% (n=31); mPFS: 3.9 m; mOS: 14.2 m NCT01631552 Notes: TNBC: triple negative breast cancer; UC: urothelial carcinoma; ORR: objective response rate; mPFS: median progression-free survival; mOS: median overall survival; pCR: pathologic complete response; SG: sacituzumab govitecan. 
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