Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Mar 13;15(6):1744.
doi: 10.3390/cancers15061744.

Overview of Trop-2 in Cancer: From Pre-Clinical Studies to Future Directions in Clinical Settings

Pasquale Lombardi  1 , Marco Filetti  1   2 , Rosa Falcone  1 , Valeria Altamura  1 , Francesco Paroni Sterbini  1 , Emilio Bria  3   4 , Alessandra Fabi  5 , Diana Giannarelli  6 , Giovanni Scambia  7   8 , Gennaro Daniele  1
Affiliations
Review

Overview of Trop-2 in Cancer: From Pre-Clinical Studies to Future Directions in Clinical Settings

Pasquale Lombardi et al. Cancers (Basel). .

Abstract

Trophoblast cell surface antigen-2 (Trop-2) is a glycoprotein that was first described as a membrane marker of trophoblast cells and was associated with regenerative abilities. Trop-2 overexpression was also described in several tumour types. Nevertheless, the therapeutic potential of Trop-2 was widely recognized and clinical studies with drug-antibody conjugates have been initiated in various cancer types. Recently, these efforts have been rewarded with the approval of sacituzumab govitecan from both the Food and Drug Administration (FDA) and European Medicines Agency (EMA), for metastatic triple-negative breast cancer patients. In our work, we briefly summarize the various characteristics of cancer cells overexpressing Trop-2, the pre-clinical activities of specific inhibitors, and the role of anti-Trop-2 therapy in current clinical practice. We also review the ongoing clinical trials to provide a snapshot of the future developments of these therapies.

Keywords: ADC; Trop-2; bystander effect; target therapy.

PubMed Disclaimer

Conflict of interest statement

E.B. received speakers’ and travel fees from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis, and Roche. E.B. received institutional research grants from Astra-Zeneca and Roche. A.F. received honoraria or speakers’ fee from Roche, Pfizer, Eli-Lilly, Novartis, Eisai, AstraZeneca, Exact Science, Epihonpharma, Daiichi-Sanlyo, Gilead, and Seagen. G.S. has served on advisory boards for TESARO Bio Italy S.r.l, Johnson & Johnson, and Clovis Oncology Italy S.r.l. He received support for travel or accommodations from MSD Italy S.r.l and Clovis Oncology Italy S.r.l, and institutional research funding from MSD Italy S.r.l. G.D. has served on the advisory board of Beigene and received support for travel and accommodations from Roche. The other authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Trop-2 membrane-associated interacting partners and signalling pathways.
See this image and copyright information in PMC

References

    1. Shvartsur A., Bonavida B. Trop2 and its overexpression in cancers: Regulation and clinical/therapeutic implications. Genes Cancer. 2015;6:84–105. doi: 10.18632/genesandcancer.40. - DOI - PMC - PubMed
    1. Lipinski M., Parks D.R., Rouse R.V., Herzenberg L.A. Human trophoblast cell-surface antigens defined by monoclonal antibodies. Proc. Natl. Acad. Sci. USA. 1981;78:5147–5150. doi: 10.1073/pnas.78.8.5147. - DOI - PMC - PubMed
    1. Trerotola M., Jernigan D.L., Liu Q., Siddiqui J., Fatatis A., Languino L.R. Trop-2 promotes prostate cancer metastasis by modulating βintegrin functions. Cancer Res. 2013;73:3155–3167. doi: 10.1158/0008-5472.CAN-12-3266. - DOI - PMC - PubMed
    1. Bignotti E., Zanotti L., Calza S., Falchetti M., Lonardi S., Ravaggi A., Romani C., Todeschini P., Bandiera E., Tassi R.A., et al. Trop-2 protein overexpression is an independent marker for predicting disease recurrence in endometrioid endometrial carcinoma. BMC Clin. Pathol. 2012;12:22. doi: 10.1186/1472-6890-12-22. - DOI - PMC - PubMed
    1. Cubas R., Zhang S., Li M., Chen C., Yao Q. Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Mol. Cancer. 2010;9:253. doi: 10.1186/1476-4598-9-253. - DOI - PMC - PubMed

Grants and funding