Improving Ovarian Cancer Therapy by a Novel Use of DFMO

Most ovarian cancer patients are diagnosed with late stage disease that is often unresponsive to existing therapies. So we need to explore other effective avenues to help relieve stress and minimize side effects. Recent approval of sipuleucel-T and YERVOY™ (ipilimumab, anti-CTLA-4) by the US Food and Drug Administration (FDA) marks the validation of immunotherapy for various cancers. Research demonstrates that the human immune system naturally recognizes and fights cancer cells as evidenced by the presence of tumor-specific killer T-cells within tumors. Particularly in ovarian cancer, higher number of tumor-specific killer T-cells within the tumor appear to be correlated with improved patient outcome. The problem is that this natural self-defense mounted by the host immune system is typically insufficient to combat cancer cell growth as ovarian cancer can escape the host immune system by fostering a highly suppressive environment in the peritoneal cavity. Thus, tilting the balance from an immune-suppressive to an immune-active environment may be necessary for effective ovarian cancer therapy. Here we will explore a novel use of difluoromethylornithine (DFMO), a FDA-approved drug therapy for African sleeping sickness, as adjuncts to tumor-specific immune therapy. We believe that DFMO may reverse tumor-induced immunosuppressive mechanisms and revokes a measurable antitumor immune response that delays ovarian cancer progression. We hope that our research will certainly open the opportunity for the rapid translation of these preclinical findings into the clinic and shed new light for the development of more effective immune-based treatments for ovarian cancer.