TROP2-targeting antibody-drug conjugates in breast cancer and ovarian carcinoma: therapeutic advances and resistance mechanisms.

Antibody-drug conjugates (ADCs) targeting trophoblast cell-surface antigen 2 (TROP2) have emerged as a promising therapeutic strategy for the treatment of triple-negative breast cancer (TNBC) and ovarian carcinoma, two malignancies characterized by poor prognosis and limited therapeutic options. ADCs are complex molecules that combine the specificity of monoclonal antibodies with the cytotoxic potency of chemotherapeutic agents, enabling selective delivery of drugs to tumor cells while minimizing systemic toxicity. Recent advances in ADC technology have led to the development of several TROP2-targeting agents, including sacituzumab govitecan and datopotamab deruxtecan, which have demonstrated significant efficacy and acceptable safety in patients with advanced or treatment-resistant TNBC and ovarian carcinoma. Clinical trials have reported improvements in progression-free and overall survival, as well as objective response rates, compared to standard therapies. However, emerging evidence indicates that both primary and acquired resistance mechanisms may limit the long-term efficacy of these agents. Current research efforts are focused on elucidating these resistance pathways, optimizing combination strategies with immunotherapy and targeted agents, and expanding the application of TROP2-targeting ADCs to other tumor types. The integration of biomarker-driven patient selection and next-generation ADC technologies offers new opportunities to overcome resistance and enhance clinical benefit. This review provides a comprehensive overview of the development, clinical implementation, and resistance mechanisms of TROP2-targeting ADCs in TNBC and ovarian carcinoma, underscoring their potential to reshape the therapeutic landscape of these challenging cancers.