Gynecologic Oncology Reports · Published 2026-06-15 · DOI 10.1016/j.gore.2026.102146
Sarah Ottum, Orazio De Tommasi, Cem Demirkiran, Stefania Bellone, Natalia Buza, Na Niu, Namrata Sethi, Tobias M. Hartwich, Alessandro D. Santin
Introduction: Low-grade serous ovarian carcinoma (LGSOC) is a rare ovarian cancer subtype with limited sensitivity to chemotherapy and modest benefit from endocrine and MEK-directed therapy. New therapeutic targets are needed. We evaluated trophoblast cell-surface antigen 2 (TROP2) expression in LGSOC and the activity of datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate, in an LGSOC patient-derived xenograft (PDX) model. Methods: TROP2 expression was assessed by immunohistochemistry in a retrospective single-center cohort of 29 LGSOC cases treated at Yale University. Antitumor activity of Dato-DXd was evaluated in a TROP2-expressing PDX model derived from a heavily pretreated patient with LGSOC resistant to chemotherapy, aromatase inhibitors, and MEK inhibitors. Results: TROP2 expression was detected in 29 of 29 cases, and 23 tumors showed moderate-to-strong expression. In vivo, Dato-DXd significantly inhibited tumor growth versus vehicle/saline control in a treatment-resistant LGSOC PDX model (p < 0.0001) without relevant toxicity. Median survival was 22 days in control animals and was not reached by day 50 in the Dato-DXd group. Conclusion: TROP2 is frequently expressed in LGSOC and may represent a therapeutically relevant target. Dato-DXd showed marked antitumor activity in a treatment-resistant LGSOC PDX model. Clinical evaluation in patients with recurrent LGSOC is warranted.
Abstract from DOAJ. Public domain (CC0 1.0).
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Ottum, S., Tommasi, O., Demirkiran, C., et al. (2026). Activity of datopotamab deruxtecan in TROP2-expressing low-grade serous ovarian cancer: a preclinical study. Gynecologic Oncology Reports. https://doi.org/10.1016/j.gore.2026.102146