FTY720 enhances the anti-tumor activity of carboplatin and tamoxifen in a patient-derived xenograft model of ovarian cancer

In vitro data demonstrate that FTY720 sensitized two drug-resistant (A2780. cp20, HeyA8. MDR) and two high-grade serous ovarian cancer cell lines (COV362, CAOV3) to carboplatin, a standard of care for patients with ovarian cancer, and to the selective estrogen receptor modulator tamoxifen. FTY720 + tamoxifen was synergistic in vitro, and combinations of FTY720 + carboplatin or + tamoxifen were more effective than each single agent in a patient-derived xenograft model of ovarian carcinoma. FTY720 + tamoxifen arrested tumor growth. FTY720 + carboplatin induced tumor regressions, with tumor volumes reduced by ∼86% compared to initial tumor volumes. Anti-tumor efficacy was concomitant with increases in intracellular proapoptotic lipid ceramide. The data suggest that FTY720 + tamoxifen or carboplatin may be effective in treating ovarian tumors.