Nectin-4-directed therapeutic repositioning augments anti-tumor efficacy in epithelial ovarian carcinoma

Nectin-4, a single pass membrane protein involved in cell adhesion, has emerged as a promising target for treating solid tumors; however, its therapeutic potential in EOC is still under investigation. In this study, we evaluate the feasibility of repurposing a Nectin-4-targeted antibody-drug conjugate (ADC) as a treatment for Nectin-4-positive EOC, and explore combination strategies to enhance therapeutic outcomes.

We demonstrate that enfortumab vedotin (EV), a clinically approved anti-Nectin-4 ADC, effectively inhibits tumor growth in Nectin-4-positive EOC models both in vitro and in vivo. Additionally, we identify acetalax, a previously approved laxative, as having efficacy against Nectin-4-positive EOC tumors. Notably, combining EV with acetalax synergistically induces tumor cell death in vitro and significantly reduces tumor relapse in vivo.