靶向TROP2在胰腺癌治疗中的潜力

李语婕; 陈颢

doi:10.19401/j.cnki.1007-3639.2022.03.010

您当前的位置：

首页 >

文章列表页 >

靶向TROP2在胰腺癌治疗中的潜力

综述 | 更新时间：2025-12-31

- 靶向TROP2在胰腺癌治疗中的潜力
- Potential of targeting TROP2 in the treatment of pancreatic cancer
- 中国癌症杂志 2022年32卷第3期页码：268-273
- 作者机构：
  
  复旦大学附属肿瘤医院中西医结合科,复旦大学上海医学院肿瘤学系,上海 200032
- 作者简介：
  
  陈颢 E-mail: chengkll@sina.com
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.03.010
  中图分类号： R735.9
- 收稿：2021-08-10，
  
  纸质出版：2022-03-30
- 稿件说明：
移动端阅览
李语婕, 陈颢. 靶向TROP2在胰腺癌治疗中的潜力[J]. 中国癌症杂志, 2022,32(3):268-273.

Yujie LI, Hao CHEN. Potential of targeting TROP2 in the treatment of pancreatic cancer[J]. China Oncology, 2022, 32(3): 268-273.
李语婕, 陈颢. 靶向TROP2在胰腺癌治疗中的潜力[J]. 中国癌症杂志, 2022,32(3):268-273. DOI： 10.19401/j.cnki.1007-3639.2022.03.010.

Yujie LI, Hao CHEN. Potential of targeting TROP2 in the treatment of pancreatic cancer[J]. China Oncology, 2022, 32(3): 268-273. DOI： 10.19401/j.cnki.1007-3639.2022.03.010.

摘要

胰腺癌是发病率高、进展速度快且生存率低的一种恶性肿瘤

临床上亟待寻找可用于精准治疗或提高预后的新靶标。近年来研究发现

滋养层细胞表面抗原2（trophoblast cell surface antigen 2

TROP2）在多种恶性肿瘤中高表达

通过细胞表面受体信号参与恶性肿瘤细胞的增殖、迁移及黏附等进展过程。概述TROP2在胰腺癌中的表达、参与介导的信号转导通路及以TROP2为靶点的抗肿瘤药物的研究进展

为靶向TROP2在胰腺癌治疗中的机制和提高胰腺癌患者预后方面提供参考。

Abstract

Pancreatic cancer is a malignant tumor with high incidence

rapid progression and low survival rate. It is in urgent need of new targets for precise treatment or improvement of prognosis. In recent years

it has been found that trophoblast cell surface antigen 2 (TROP2) is highly expressed in a variety of malignant tumors and participates in the progress of proliferation

migration and adhesion of malignant tumor cells through cell surface receptor signals. In this paper

the expression of TROP2 in pancreatic cancer

the signaling pathway involved in the mediation of TROP2 and the research progress of antitumor drugs targeting TROP2 were summarized

which provided some references for the mechanism of targeting TROP2 in the treatment of pancreatic cancer and the improvement of prognosis of patients.

关键词

Keywords

references

SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 . DOI: 10.3322/caac.v71.3 http://doi.org/10.3322/caac.v71.3 https://onlinelibrary.wiley.com/toc/15424863/71/3 https://onlinelibrary.wiley.com/toc/15424863/71/3

DROUILLARD A , MANFREDI S , LEPAGE C , et al . Epidemiology of pancreatic cancer [J ] . Bull Du Cancer , 2018 , 105 ( 1 ): 63 - 69 . DOI: 10.1016/j.bulcan.2017.11.004 http://doi.org/10.1016/j.bulcan.2017.11.004 https://linkinghub.elsevier.com/retrieve/pii/S000745511730365X https://linkinghub.elsevier.com/retrieve/pii/S000745511730365X

GIOVANNETTI E , VAN DER BORDEN C L , FRAMPTON A E , et al . Never let it go: stopping key mechanisms underlying metastasis to fight pancreatic cancer [J ] . Semin Cancer Biol , 2017 , 44 : 43 - 59 . DOI: 10.1016/j.semcancer.2017.04.006 http://doi.org/10.1016/j.semcancer.2017.04.006 https://linkinghub.elsevier.com/retrieve/pii/S1044579X17300998 https://linkinghub.elsevier.com/retrieve/pii/S1044579X17300998

CARIOLI G , MALVEZZI M , BERTUCCIO P , et al . European cancer mortality predictions for the year 2021 with focus on pancreatic and female lung cancer [J ] . Ann Oncol , 2021 , 32 ( 4 ): 478 - 487 . DOI: 10.1016/j.annonc.2021.01.006 http://doi.org/10.1016/j.annonc.2021.01.006 https://linkinghub.elsevier.com/retrieve/pii/S0923753421000144 https://linkinghub.elsevier.com/retrieve/pii/S0923753421000144

FERLAY J , PARTENSKY C , BRAY F . More deaths from pancreatic cancer than breast cancer in the EU by 2017 [J ] . Acta Oncol , 2016 , 55 ( 9/10 ): 1158 - 1160 . DOI: 10.1080/0284186X.2016.1197419 http://doi.org/10.1080/0284186X.2016.1197419 https://www.tandfonline.com/doi/full/10.1080/0284186X.2016.1197419 https://www.tandfonline.com/doi/full/10.1080/0284186X.2016.1197419

RAHIB L , SMITH B D , AIZENBERG R , et al . Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States [J ] . Cancer Res , 2014 , 74 ( 11 ): 2913 - 2921 . DOI: 10.1158/0008-5472.CAN-14-0155 http://doi.org/10.1158/0008-5472.CAN-14-0155 http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.CAN-14-0155 http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.CAN-14-0155

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 ( 3 ): 645 - 656 . DOI: 10.1002/mol2.v14.3 http://doi.org/10.1002/mol2.v14.3 https://onlinelibrary.wiley.com/toc/18780261/14/3 https://onlinelibrary.wiley.com/toc/18780261/14/3

ZAMAN S , JADID H , DENSON A C , et al . Targeting Trop-2 in solid tumors: future prospects [J ] . Onco Targets Ther , 2019 , 12 : 1781 - 1790 . DOI: 10.2147/OTT http://doi.org/10.2147/OTT https://www.dovepress.com/oncotargets-and-therapy-journal https://www.dovepress.com/oncotargets-and-therapy-journal

LENÁRT S , LENÁRT P , ŠMARDA J , et al . Trop2: jack of all trades, master of none [J ] . Cancers (Basel) , 2020 , 12 ( 11 ): E3328 .

BARDIA A , MESSERSMITH W A , KIO E A , et al . Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase Ⅰ/Ⅱ IMMU-132-01 basket trial [J ] . Ann Oncol , 2021 , 32 ( 6 ): 746 - 756 . DOI: 10.1016/j.annonc.2021.03.005 http://doi.org/10.1016/j.annonc.2021.03.005 https://linkinghub.elsevier.com/retrieve/pii/S0923753421008838 https://linkinghub.elsevier.com/retrieve/pii/S0923753421008838

张玉洁 , 孙怡琳 , 朱苹 , 等 . 人肿瘤关联钙信号转导因子2的生物信息学分析 [J ] . 医学研究生学报 , 2020 , 33 ( 6 ): 570 - 576 .

ZHANG Y J , SUN Y L , ZHU P , et al . Bioinformatic analysis of the structure and function of human TACSTD2 [J ] . J Med Postgrad , 2020 , 33 ( 6 ): 570 - 576 .

周童 , 张远鹏 , 张启文 . 靶向抑制 TROP 2基因表达对胰腺癌细胞生物学特性的影响研究 [J ] . 癌症进展 , 2018 , 16 ( 3 ): 290 - 294 .

ZHOU T , ZHANG Y P , ZHANG Q W . Effect of targeted inhibition of TROP 2 gene expression on the biological characteristics of pancreatic cancer cells [J ] . Oncol Prog , 2018 , 16 ( 3 ): 290 - 294 .

CARDILLO T M , GOVINDAN S V , SHARKEY R M , et al . Sacituzumab govitecan (IMMU-132), an anti-trop-2/SN-38 antibody-drug conjugate: characterization and efficacy in pancreatic, gastric, and other cancers [J ] . Bioconjug Chem , 2015 , 26 ( 5 ): 919 - 931 . DOI: 10.1021/acs.bioconjchem.5b00223 http://doi.org/10.1021/acs.bioconjchem.5b00223 https://pubs.acs.org/doi/10.1021/acs.bioconjchem.5b00223 https://pubs.acs.org/doi/10.1021/acs.bioconjchem.5b00223

CUBAS R , ZHANG S , LI M , et al . Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway [J ] . Mol Cancer , 2010 , 9 : 253 . DOI: 10.1186/1476-4598-9-253 http://doi.org/10.1186/1476-4598-9-253 https://doi.org/10.1186/1476-4598-9-253 https://doi.org/10.1186/1476-4598-9-253

LI X X , TENG S F , ZHANG Y Y , et al . TROP2 promotes proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT [J ] . Oncotarget , 2017 , 8 ( 29 ): 47052 - 47063 . DOI: 10.18632/oncotarget.v8i29 http://doi.org/10.18632/oncotarget.v8i29 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.v8i29 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.v8i29

ZHAO W , JIA L , KUAI X , et al . The role and molecular mechanism of Trop2 induced epithelial-mesenchymal transition through mediated β-catenin in gastric cancer [J ] . Cancer Med , 2019 , 8 ( 3 ): 1135 - 1147 . DOI: 10.1002/cam4.2019.8.issue-3 http://doi.org/10.1002/cam4.2019.8.issue-3 https://onlinelibrary.wiley.com/toc/20457634/8/3 https://onlinelibrary.wiley.com/toc/20457634/8/3

GUERRA E , TREROTOLA M , RELLI V , et al . Trop-2 induces ADAM10-mediated cleavage of E-cadherin and drives EMT-less metastasis in colon cancer [J ] . Neoplasia , 2021 , 23 ( 9 ): 898 - 911 . DOI: 10.1016/j.neo.2021.07.002 http://doi.org/10.1016/j.neo.2021.07.002 https://linkinghub.elsevier.com/retrieve/pii/S1476558621000567 https://linkinghub.elsevier.com/retrieve/pii/S1476558621000567

SUN X T , XING G Y , ZHANG C , et al . Knockdown of Trop2 inhibits proliferation and migration and induces apoptosis of endometrial cancer cells via AKT/β-catenin pathway [J ] . Cell Biochem Funct , 2020 , 38 ( 2 ): 141 - 148 . DOI: 10.1002/cbf.v38.2 http://doi.org/10.1002/cbf.v38.2 https://onlinelibrary.wiley.com/toc/10990844/38/2 https://onlinelibrary.wiley.com/toc/10990844/38/2

ZHAO W , KUAI X W , ZHOU X Y , et al . Trop2 is a potential biomarker for the promotion of EMT in human breast cancer [J ] . Oncol Rep , 2018 , 40 ( 2 ): 759 - 766 .

LIU T , LIU Y Y , BAO X X , et al . Overexpression of TROP2 predicts poor prognosis of patients with cervical cancer and promotes the proliferation and invasion of cervical cancer cells by regulating ERK signaling pathway [J ] . PLoS One , 2013 , 8 ( 9 ): e75864 . DOI: 10.1371/journal.pone.0075864 http://doi.org/10.1371/journal.pone.0075864 https://dx.plos.org/10.1371/journal.pone.0075864 https://dx.plos.org/10.1371/journal.pone.0075864

GUAN H Y , GUO Z J , LIANG W W , et al . Trop2 enhances invasion of thyroid cancer by inducing MMP2 through ERK and JNK pathways [J ] . BMC Cancer , 2017 , 17 ( 1 ): 486 . DOI: 10.1186/s12885-017-3475-2 http://doi.org/10.1186/s12885-017-3475-2 http://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3475-2 http://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3475-2

HOU J B , LV A , DENG Q , et al . TROP2 promotes the proliferation and metastasis of glioblastoma cells by activating the JAK2/STAT3 signaling pathway [J ] . Oncol Rep , 2019 , 41 ( 2 ): 753 - 764 .

TANG G X , TANG Q , JIA L Z , et al . TROP2 increases growth and metastasis of human oral squamous cell carcinoma through activation of the PI3K/AKT signaling pathway [J ] . Int J Mol Med , 2019 , 44 ( 6 ): 2161 - 2170 .

仇金荣 , 唐奇 , 林红 , 等 . 人滋养层细胞表面抗原2在人胰腺癌中的表达及其临床意义 [J ] . 中华医学杂志 , 2011 , 91 ( 2 ): 103 - 106 .

QIU J R , TANG Q , LIN H , et al . Expression and clinical significance of Trop-2 in human pancreatic cancer [J ] . Natl Med J China , 2011 , 91 ( 2 ): 103 - 106 .

FONG D , MOSER P , KRAMMEL C , et al . High expression of TROP2 correlates with poor prognosis in pancreatic cancer [J ] . Br J Cancer , 2008 , 99 ( 8 ): 1290 - 1295 . DOI: 10.1038/sj.bjc.6604677 http://doi.org/10.1038/sj.bjc.6604677 https://doi.org/10.1038/sj.bjc.6604677 https://doi.org/10.1038/sj.bjc.6604677

SHVARTSUR A , BONAVIDA B . Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications [J ] . Genes Cancer , 2015 , 6 ( 3/4 ): 84 - 105 . DOI: 10.18632/genesandcancer.v6i3-4 http://doi.org/10.18632/genesandcancer.v6i3-4 https://www.genesandcancer.com/lookup/doi/10.18632/genesandcancer.v6i3-4 https://www.genesandcancer.com/lookup/doi/10.18632/genesandcancer.v6i3-4

MCDOUGALL A R A , TOLCOS M , HOOPER S B , et al . Trop2: from development to disease [J ] . Dev Dyn , 2015 , 244 ( 2 ): 99 - 109 . DOI: 10.1002/dvdy.v244.2 http://doi.org/10.1002/dvdy.v244.2 http://doi.wiley.com/10.1002/dvdy.v244.2 http://doi.wiley.com/10.1002/dvdy.v244.2

MORI Y , AKITA K , OJIMA K , et al . Trophoblast cell surface antigen 2 (Trop-2) phosphorylation by protein kinase C α/δ (PKCα/δ) enhances cell motility [J ] . J Biol Chem , 2019 , 294 ( 30 ): 11513 - 11524 . DOI: 10.1074/jbc.RA119.008084 http://doi.org/10.1074/jbc.RA119.008084 https://linkinghub.elsevier.com/retrieve/pii/S0021925820306542 https://linkinghub.elsevier.com/retrieve/pii/S0021925820306542

于群 , 苗庆芳 . 抗肿瘤药物靶点Trop2研究进展 [J ] . 中国医药生物技术 , 2018 , 13 ( 4 ): 353 - 357 .

YU Q , MIAO Q F . Research progress in antitumor molecular target Trop2 [J ] . Chin Med Biotechnol , 2018 , 13 ( 4 ): 353 - 357 .

GUERRA E , TREROTOLA M , TRIPALDI R , et al . Trop-2 induces tumor growth through AKT and determines sensitivity to AKT inhibitors [J ] . Clin Cancer Res , 2016 , 22 ( 16 ): 4197 - 4205 . DOI: 10.1158/1078-0432.CCR-15-1701 http://doi.org/10.1158/1078-0432.CCR-15-1701 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-15-1701 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-15-1701

IKEDA M , YAMAGUCHI M , KATO K , et al . Pr1E11, a novel anti-TROP-2 antibody isolated by adenovirus-based antibody screening, recognizes a unique epitope [J ] . Biochem Biophys Res Commun , 2015 , 458 ( 4 ): 877 - 882 . DOI: 10.1016/j.bbrc.2015.02.051 http://doi.org/10.1016/j.bbrc.2015.02.051 https://linkinghub.elsevier.com/retrieve/pii/S0006291X1500279X https://linkinghub.elsevier.com/retrieve/pii/S0006291X1500279X

SHARKEY R M , MCBRIDE W J , CARDILLO T M , et al . Enhanced delivery of SN-38 to human tumor xenografts with an anti-trop-2-SN-38 antibody conjugate (sacituzumab govitecan) [J ] . Clin Cancer Res , 2015 , 21 ( 22 ): 5131 - 5138 . DOI: 10.1158/1078-0432.CCR-15-0670 http://doi.org/10.1158/1078-0432.CCR-15-0670 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-15-0670 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-15-0670

WAHBY S , FASHOYIN-AJE L , OSGOOD C L , et al . FDA approval summary: accelerated approval of sacituzumab govitecan-hziy for third-line treatment of metastatic triple-negative breast cancer [J ] . Clin Cancer Res , 2021 , 27 ( 7 ): 1850 - 1854 . DOI: 10.1158/1078-0432.CCR-20-3119 http://doi.org/10.1158/1078-0432.CCR-20-3119 https://aacrjournals.org/clincancerres/article/27/7/1850/671880/FDA-Approval-Summary-Accelerated-Approval-of https://aacrjournals.org/clincancerres/article/27/7/1850/671880/FDA-Approval-Summary-Accelerated-Approval-of

CRISCITIELLO C , MORGANTI S , CURIGLIANO G . Antibody-drug conjugates in solid tumors: a look into novel targets [J ] . J Hematol Oncol , 2021 , 14 ( 1 ): 20 . DOI: 10.1186/s13045-021-01035-z http://doi.org/10.1186/s13045-021-01035-z https://doi.org/10.1186/s13045-021-01035-z https://doi.org/10.1186/s13045-021-01035-z

BARDIA A , TOLANEY S M , PUNIE K , et al . Biomarker analyses in the phase Ⅲ ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer [J ] . Ann Oncol , 2021 , 32 ( 9 ): 1148 - 1156 . DOI: 10.1016/j.annonc.2021.06.002 http://doi.org/10.1016/j.annonc.2021.06.002 https://linkinghub.elsevier.com/retrieve/pii/S0923753421020470 https://linkinghub.elsevier.com/retrieve/pii/S0923753421020470

BARDIA A , HURVITZ S A , TOLANEY S M , et al . Sacituzumab govitecan in metastatic triple-negative breast cancer [J ] . N Engl J Med , 2021 , 384 ( 16 ): 1529 - 1541 . DOI: 10.1056/NEJMoa2028485 http://doi.org/10.1056/NEJMoa2028485 http://www.nejm.org/doi/10.1056/NEJMoa2028485 http://www.nejm.org/doi/10.1056/NEJMoa2028485

STROP P , TRAN T T , DORYWALSKA M , et al . RN927C, a site-specific trop-2 antibody-drug conjugate (ADC) with enhanced stability, is highly efficacious in preclinical solid tumor models [J ] . Mol Cancer Ther , 2016 , 15 ( 11 ): 2698 - 2708 . DOI: 10.1158/1535-7163.MCT-16-0431 http://doi.org/10.1158/1535-7163.MCT-16-0431 http://mct.aacrjournals.org/lookup/doi/10.1158/1535-7163.MCT-16-0431 http://mct.aacrjournals.org/lookup/doi/10.1158/1535-7163.MCT-16-0431

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 ( 12 ): 2329 - 2340 . DOI: 10.1158/1535-7163.MCT-21-0206 http://doi.org/10.1158/1535-7163.MCT-21-0206 http://mct.aacrjournals.org/lookup/doi/10.1158/1535-7163.MCT-21-0206 http://mct.aacrjournals.org/lookup/doi/10.1158/1535-7163.MCT-21-0206

MAO Y , WANG X Y , ZHENG F , et al . The tumor-inhibitory effectiveness of a novel anti-Trop2 Fab conjugate in pancreatic cancer [J ] . Oncotarget , 2016 , 7 ( 17 ): 24810 - 24823 . DOI: 10.18632/oncotarget.v7i17 http://doi.org/10.18632/oncotarget.v7i17 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.v7i17 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.v7i17

ROSSI E A , ROSSI D L , CARDILLO T M , et al . Redirected T-cell killing of solid cancers targeted with an anti-CD3/Trop-2-bispecific antibody is enhanced in combination with interferon-α [J ] . Mol Cancer Ther , 2014 , 13 ( 10 ): 2341 - 2351 . DOI: 10.1158/1535-7163.MCT-14-0345 http://doi.org/10.1158/1535-7163.MCT-14-0345 http://mct.aacrjournals.org/lookup/doi/10.1158/1535-7163.MCT-14-0345 http://mct.aacrjournals.org/lookup/doi/10.1158/1535-7163.MCT-14-0345

CHEN H P , WEI F J , YIN M , et al . CD27 enhances the killing effect of CAR-T cells targeting trophoblast cell surface antigen 2 in the treatment of solid tumors [J ] . Cancer Immunol Immunother , 2021 , 70 ( 7 ): 2059 - 2071 . DOI: 10.1007/s00262-020-02838-8 http://doi.org/10.1007/s00262-020-02838-8 https://doi.org/10.1007/s00262-020-02838-8 https://doi.org/10.1007/s00262-020-02838-8

NISHIMURA T , MITSUNAGA M , SAWADA R , et al . Photoimmunotherapy targeting biliary-pancreatic cancer with humanized anti-TROP2 antibody [J ] . Cancer Med , 2019 , 8 ( 18 ): 7781 - 7792 . DOI: 10.1002/cam4.v8.18 http://doi.org/10.1002/cam4.v8.18 https://onlinelibrary.wiley.com/toc/20457634/8/18 https://onlinelibrary.wiley.com/toc/20457634/8/18

浏览量

4289

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

胰腺癌精准治疗：从小众走向主流

着丝粒蛋白A驱动的染色体不稳定性与乳腺癌相关性研究的进展及展望：机制、预后及临床靶向治疗应用

靶向治疗及免疫治疗联合化疗为产AFP阳性结肠癌患者带来显著获益1例病例报告并文献复习

转移性结直肠癌三线治疗的研究现状及进展

卡瑞利珠单抗联合化疗及靶向治疗在复发、转移及初治晚期宫颈癌中的疗效与安全性分析：一项回顾性队列研究