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2025, 09, v.34 1296-1301
Trop-2在妇科恶性肿瘤中的表达特征及其靶向治疗应用研究进展
基金项目(Foundation): 北京市希思科临床肿瘤学研究基金会(Y-Gilead2024-ZD-0082); 国家临床重点专科建设项目(U114000)
邮箱(Email): fengfz1969@sina.com;
DOI:
投稿时间: 2025-02-06
投稿日期(年): 2025
修回时间: 2025-04-10
终审时间: 2025-08-06
终审日期(年): 2025
审稿周期(年): 1
发布时间: 2025-09-15
出版时间: 2025-09-15
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摘要:

近年来研究发现,滋养层细胞表面抗原2(Trop-2)是妇科恶性肿瘤发生、发展过程中重要的靶点分子,其异常表达对肿瘤增殖、侵袭、转移等恶性生物学行为起到调控作用,同时与肿瘤免疫微环境的调控密切相关。以抗体偶联药物为主的抗Trop-2治疗在表达Trop-2的多种难治性实体瘤中展现出显著且持久的疾病缓解能力,对卵巢癌、宫颈癌及子宫内膜癌的疗效同样显著。这些研究或将为晚期、复发性妇科恶性肿瘤带来新的治疗方法。本文综述了Trop-2的功能及其在常见妇科恶性肿瘤中的表达情况、作用及相关靶向治疗的最新进展,以期启发临床对妇科恶性肿瘤治疗策略制定的再思考。

Abstract:

Recent studies have shown that trophoblast cell surface antigen 2(Trop-2)is an important target molecule in the occurrence and development of gynecologic malignancies.Its abnormal expression regulates malignant biological behaviors such as tumor proliferation,invasion,and metastasis,and is closely related to the regulation of tumor immune microenvironment.Anti-Trop-2therapy,primarily antibody-drug conjugates,has demonstrated significant and durable disease remission in various refractory solid tumors expressing Trop-2,with similarly remarkable efficacy in ovarian,cervical,and endometrial cancers.These studies may bring new treatment options for advanced and recurrent gynecologic malignancies.This review summarizes the functions of Trop-2,its expression patterns in common gynecologic malignancies,its roles,and the latest progress in related targeted therapies,aiming to inspire reconsideration of treatment strategies for gynecologic malignancies in clinical practice.

参考文献

[1] Koltai T,Fliegel L. The relationship between Trop-2,chemotherapeutic drugs,and chemoresistance[J].Int J Mol Sci,2023,25:87.

[2] Qiu S,Zhang J,Wang Z,et al.Targeting Trop-2in cancer:recent research progress and clinical application[J].Biochim Biophys Acta Rev Cancer,2023,1878:188902.

[3] Tymon-Rosario J, Gorman M, Richardson DL,et al.Advances in antibody-drug conjugates for gynecologic malignancies[J].Curr Opin Obstet Gynecol,2023,35:6-14.

[4] Wen Y,Ouyang D,Zou Q,et al.A literature review of the promising future of TROP2:apotential drug therapy target[J].Ann Transl Med,2022,10:1403.

[5] Hou J,Lv A,Deng Q,et al. TROP2 promotes the proliferation and metastasis of glioblastoma cells by activating the JAK2/STAT3signaling pathway[J].Oncol Rep,2019,41:753-764.

[6] Tang G,Tang Q,Jia L,et al.TROP2increases growth and metastasis of human oral squamous cell carcinoma through activation of the PI3K/Akt signaling pathway[J].Int J Mol Med,2019,44:2161-2170.

[7] Stoyanova T,Goldstein AS,Cai H,et al. Regulated proteolysis of Trop2drives epithelial hyperplasia and stem cell self-renewal viaβ-catenin signaling[J].Genes Dev,2012,26:2271-2285.

[8] Wu B,Yu C,Zhou B,et al. Overexpression of TROP2promotes proliferation and invasion of ovarian cancer cells[J].Exp Ther Med,2017,14:1947-1952.

[9] Sun X,Xing G,Zhang C,et al.Knockdown of Trop2inhibits proliferation and migration and induces apoptosis of endometrial cancer cells via AKT/β-catenin pathway[J].Cell Biochem Funct,2020,38:141-148.

[10] Liu T,Liu Y,Bao X,et al. Overexpression of TROP2predicts poor prognosis of patients with cervical cancer and promotes the proliferation and invasion of cervical cancer cells by regulating ERK signaling pathway[J/OL].PLoS One,2013,8:e75864.

[11] Salerno EP,Bedognetti D, Mauldin IS,et al. Human melanomas and ovarian cancers overexpressing mechanical barrier molecule genes lack immune signatures and have increased patient mortality risk[J].Oncoimmunology,2016,5:e1240857.

[12] Bessede A,Peyraud F,Besse B,et al.TROP2is associated with primary resistance to immune checkpoint inhibition in patients with advanced non-Small cell lung cancer[J].Clin Cancer Res,2024,30:779-785.

[13] Morgenstern-Kaplan D,Kareff SA, Trabolsi A,et al.Genomic,immunologic,and prognostic associations of TROP2(TACSTD2)expression in solid tumors[J].Oncologist,2024,29:e1480-e1491.

[14] Wang X,Long M,Dong K,et al.Chemotherapy agentsinduced immunoresistance in lung cancer cells could be reversed by trop-2inhibition in vitro and in vivo by interaction with MAPK signaling pathway[J].Cancer Biol Ther,2013,14:1123-1132.

[15] Chiba Y,Kojima Y,Yazaki S,et al.Trop-2expression and the tumor immune microenvironment in cervical cancer[J].Gynecol Oncol,2024,187:51-57.

[16] Lai J,Deng S,Cao J,et al.Identification of biomarker associated with Trop2 in breast cancer:implication for targeted therapy[J].Discov Oncol,2024,15:413.

[17] Anastasio MK,Shuey S,Davidson BA. Antibody-drug conjugates in gynecologic cancers[J].Curr Treat Options Oncol,2024,25:1-19.

[18]乔山峰,张春艳,丁小丽,等.高级别浆液性卵巢癌患者血清CD26、CD109与临床病理特征和预后的关系研究[J].生殖医学杂志,2024,33:907-912.

[19] Han X,Gao Y,Jiang M,et al. Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2in high-grade serous ovarian cancer[J].J Cancer,2024,15:3427-3440.

[20]冯倩倩,卢丹.TROP2在宫颈病变中的表达及临床研究[J].实用妇科内分泌电子杂志,2020,7:53-57.

[21] Bignotti E,Zanotti L,Calza S,et al. Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma[J].BMC Clin Pathol,2012,12:22.

[22] FucàG,Sabatucci I,Paderno M,et al.The clinical landscape of antibody-drug conjugates in endometrial cancer[J].Int J Gynecol Cancer,2024,34:1795-1804.

[23]龙腾飞,程玲慧,王彦,等.人滋养细胞表面抗原(Trop-2)在病变子宫内膜中表达的研究[J].现代生物医学进展,2020,20:4793-4796.

[24] Bignotti E,Todeschini P,Calza S,et al.Trop-2overexpression as an independent marker for poor overall survival in ovarian carcinoma patients[J].Eur J Cancer,2010,46:944-953.

[25]杨旭峰,雷龙春,成争艳.宫颈鳞癌组织TROP2蛋白的表达特点及其与预后的相关性[J].临床与病理杂志,2018,38:2371-2377.

[26] Pavone G,Motta L,Martorana F,et al.A new kid on the block:sacituzumab govitecan for the treatment of breast cancer and other solid tumors[J].Molecules,2021,26:7294.

[27] Perrone E,Lopez S,Zeybek B,et al.Preclinical activity of sacituzumab govitecan,an antibody-drug conjugate targeting trophoblast cell-surface antigen 2(Trop-2)linked to the active metabolite of irinotecan(SN-38),in ovarian cancer[J].Front Oncol,2020,10:118.

[28] Zeybek B,Manzano A,Bianchi A,et al.Cervical carcinomas that overexpress human trophoblast cell-surface marker(Trop-2)are highly sensitive to the antibody-drug conjugate sacituzumab govitecan[J].Sci Rep,2020,10:973.

[29] Perrone E,Manara P,Lopez S,et al.Sacituzumab govitecan,an antibody-drug conjugate targeting trophoblast cell-surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas in vitro and in vivo[J].Mol Oncol,2020,14:645-656.

[30] Santin AD,Corr BR,Spira A,et al.Efficacy and safety of sacituzumab govitecan in patients with advanced solid tumors(TROPiCS-03):analysis in patients with advanced endometrial cancer[J].J Clin Oncol,2024,42:3421-3429.

[31] An J,Li G,Zhang Y,et al.Sacituzumab govitecan for Chinese patients with recurrent/metastatic cervical cancer:interim analysis of the phase II basket study EVER-132-003[J].Gynecol Oncol,2024,190:S22.

[32] Okajima D,Yasuda S,Maejima T,et al. Datopotamab deruxtecan,a novel TROP2-directed antibody-drug conjugate,demonstrates potent antitumor activity by efficient drug delivery to tumor cells[J]. Mol Cancer Ther,2021,20:2329-2340.

[33] McNamara B,Greenman M,Bellone S,et al. Preclinical activity of datopotamab deruxtecan,a novel TROP2directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2(TROP2)in ovarian carcinoma[J].Gynecol Oncol,2024,189:16-23.

[34] Oaknin A,Ang JE,Rha SY,et al.714MO Datopotamab deruxtecan(Dato-DXd)in patients with endometrial(EC)or ovarian cancer(OC):Results from the phase II TROPIONPanTumor03study[J].Ann Oncol,2024,35:S547-S548.

[35] Wang D,Wang K,An R,et al.715MO Safety and efficacy of sacituzumab tirumotecan(sac-TMT)in patients(pts)with previously treated advanced endometrial carcinoma(EC)and ovarian cancer(OC)from a phaseⅡstudy[J].Ann Oncol,2024,35:S548.

[36] Wang J,An R,Huang Y,et al.716MO Efficacy and safety of sacituzumab tirumotecan(sac-TMT)plus pembrolizumab in patients with recurrent or metastatic cervical cancer[J].Ann Oncol,2024,35:S548-S549.

[37] Coates JT,Sun S,Leshchiner I,et al. Parallel genomic alterations of antigen and payload targets mediate polyclonal acquired clinical resistance to sacituzumab govitecan in triplenegative breast cancer[J]. Cancer Discov,2021,11:2436-2445.

[38] Jo A,Shoji T,Otsuka H,et al.Treatment strategies for advanced and recurrent endometrial cancer using immune checkpoint inhibitors[J].Int J Clin Oncol,2025,30:229-240.

[39] Shang X,Su H,Chen X,et al.Low-dose lenvatinib and antiprogrammed cell death protein-1 combination therapy in patients with heavily pre-treated recurrent ovarian and endometrial cancer:apilot study[J].Int J Gynecol Cancer,2024,34:1203-1210.

[40] Chung YM,Khan PP,Wang H,et al.Sensitizing tumors to anti-PD-1therapy by promoting NK and CD8+T cells via pharmacological activation of FOXO3[J].J Immunother Cancer,2021,9:e002772.

[41] Cardillo TM,Sharkey RM,Rossi DL,et al. Synthetic lethality exploitation by an anti-Trop-2-SN-38antibody-drug conjugate,IMMU-132,plus PARP inhibitors in BRCA1/2-wild-type triple-negative breast cancer[J].Clin Cancer Res,2017,23:3405-3415.

基本信息:

中图分类号:R737.3

引用信息:

[1]苏昊,冯凤芝.Trop-2在妇科恶性肿瘤中的表达特征及其靶向治疗应用研究进展[J].生殖医学杂志,2025,34(09):1296-1301.

基金信息:

北京市希思科临床肿瘤学研究基金会(Y-Gilead2024-ZD-0082); 国家临床重点专科建设项目(U114000)

投稿时间:

2025-02-06

投稿日期(年):

2025

修回时间:

2025-04-10

终审时间:

2025-08-06

终审日期(年):

2025

审稿周期(年):

1

发布时间:

2025-09-15

出版时间:

2025-09-15

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