Photodynamic therapy-based combination regimen with EP4 inhibitors attenuates metastatic behavior in ovarian cancer

Ovarian cancer typically spreads throughout the peritoneal cavity, and despite standard of care treatments (surgical debulking and chemotherapy), the five-year relative survival rate remains below 50%. The use of antibody-photosensitizer conjugates (photoimmunotherapy) has emerged as a promising modality to achieve targeted photosensitizer delivery to ovarian cancer cells. In this study, we investigate epithelial growth factor (EGFR)-targeted PIT coupled with inhibition of prostaglandin E2 receptor 4 (EP4), a G-coupled-receptor that contributes to cancer progression and intracellularly transactivates EGFR. This potent triple combination significantly attenuates the metastatic behavior of ovarian cancer cells through simultaneously inducing photochemical damage and modulating protein expression.