Emerging trophoblast cell-surface antigen 2-targeting antibody-drug conjugates in gynecological cancers
Abstract
Trophoblast cell surface antigen 2 (TROP-2) is a transmembrane glycoprotein involved in intracellular signaling pathways that regulate cancer proliferation, invasion, and survival. TROP-2 is minimally expressed in normal tissues but widely overexpressed in epithelial malignancies, including breast, lung, pancreatic, bladder, and gynecologic cancers. Notably, high levels of TROP-2 RNA and protein expression have been reported in endometrial, ovarian, and cervical cancers, supporting its role in tumor progression and its potential value as a therapeutic target. Recent developments have identified TROP-2 as a promising target for antibody-drug conjugates (ADC)s, particularly in advanced or recurrent gynecologic malignancies where therapeutic resistance remains a major clinical challenge. Although immunotherapy, Poly (ADP-ribose) polymerase (PARP) inhibitors and chemotherapy have shown efficacy in subsets of patients, a significant unmet need persists, especially in those previously treated with platinum-based regimens and immune checkpoint inhibitors. Encouraging preclinical data and early-phase clinical trials have prompted the investigation of several anti-TROP-2 ADCs, including sacituzumab govitecan, datopotamab deruxtecan, and sacituzumab tirumotecan. These agents leverage the selective expression of TROP-2 on tumor cells to deliver cytotoxic payloads, while also demonstrating a bystander effect that extends activity to antigen-negative cells. Their clinical application is currently being explored in gynecologic settings. In this review, we provide an overview of TROP-2’s biological role and its relevance as a prognostic and predictive biomarker in gynecologic cancers. We further summarize the available clinical data on TROP-2-targeting ADCs and discuss future perspectives for integrating these agents into therapeutic strategies aimed at improving outcomes in ovarian, endometrial, and cervical cancers.
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BibTeX
@article{perri2026emerging,
title = {{Emerging trophoblast cell-surface antigen 2-targeting antibody-drug conjugates in gynecological cancers}},
author = {Erica Perri and Maria Rosaria Lamia and Carmela Pisano and Sabrina Chiara Cecere and Marilena Di Napoli and Lorenzo Lobianco and Sabrina Rossetti and Rosa Tambaro and Jole Ventriglia and Chiara D’Alessio and Elisabetta Coppola and Emilia Scarpa and Giovanni Pacifico and Vincenzo Terrano and Sandro Pignata and Anna Passarelli},
journal = {Frontiers in Oncology},
year = {2026},
month = nov,
doi = {10.3389/fonc.2026.2005008},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.2005008},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Emerging trophoblast cell-surface antigen 2-targeting antibody-drug conjugates in gynecological cancers
AU - Erica Perri
AU - Maria Rosaria Lamia
AU - Carmela Pisano
AU - Sabrina Chiara Cecere
AU - Marilena Di Napoli
AU - Lorenzo Lobianco
AU - Sabrina Rossetti
AU - Rosa Tambaro
AU - Jole Ventriglia
AU - Chiara D’Alessio
AU - Elisabetta Coppola
AU - Emilia Scarpa
AU - Giovanni Pacifico
AU - Vincenzo Terrano
AU - Sandro Pignata
AU - Anna Passarelli
PY - 2026
DA - 2026/11/09
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.2005008
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.2005008
AB - Trophoblast cell surface antigen 2 (TROP-2) is a transmembrane glycoprotein involved in intracellular signaling pathways that regulate cancer proliferation, invasion, and survival. TROP-2 is minimally expressed in normal tissues but widely overexpressed in epithelial malignancies, including breast, lung, pancreatic, bladder, and gynecologic cancers. Notably, high levels of TROP-2 RNA and protein expression have been reported in endometrial, ovarian, and cervical cancers, supporting its role in tumor progression and its potential value as a therapeutic target. Recent developments have identified TROP-2 as a promising target for antibody-drug conjugates (ADC)s, particularly in advanced or recurrent gynecologic malignancies where therapeutic resistance remains a major clinical challenge. Although immunotherapy, Poly (ADP-ribose) polymerase (PARP) inhibitors and chemotherapy have shown efficacy in subsets of patients, a significant unmet need persists, especially in those previously treated with platinum-based regimens and immune checkpoint inhibitors. Encouraging preclinical data and early-phase clinical trials have prompted the investigation of several anti-TROP-2 ADCs, including sacituzumab govitecan, datopotamab deruxtecan, and sacituzumab tirumotecan. These agents leverage the selective expression of TROP-2 on tumor cells to deliver cytotoxic payloads, while also demonstrating a bystander effect that extends activity to antigen-negative cells. Their clinical application is currently being explored in gynecologic settings. In this review, we provide an overview of TROP-2’s biological role and its relevance as a prognostic and predictive biomarker in gynecologic cancers. We further summarize the available clinical data on TROP-2-targeting ADCs and discuss future perspectives for integrating these agents into therapeutic strategies aimed at improving outcomes in ovarian, endometrial, and cervical cancers.
SN - 2234-943X
ER -