A New Antidiabetes Drug as a Novel Therapy for Epithelial Ovarian Cancer
Abstract
Ovarian tumors are the most lethal of all female reproductive cancers, with over 70% patient mortality within 5 years of diagnosis. Unlike most other types of cancers, there has been no improvement in survival rates for ovarian cancer patients over the past 50 years, despite ongoing advances in surgery and drug therapies. Better understanding of the causes underlying ovarian cancer progression is necessary to improve therapeutic options and subsequent patient outcomes from this deadly disease. Immunity is a key component in the pathology of many types of cancers, and it is very well established that a proper immune response is an important part of the body s anti-tumor defenses. We recently discovered that a protein called "CXCL10," normally a strong signal for white blood cells to infiltrate and attack tumor tissue, is modified in ovarian tumors. Modified CXCL10 acts as an "off switch," shutting down the antitumor immune response. As a consequence, white blood cells are unable to attack the tumor efficiently, and the tumor can grow and proliferate unchallenged. Crucial to this process is another protein called "DPP4," which acts as the trigger to modify CXCL10. Importantly, DPP4 can be targeted by an existing drug -- Sitagliptin (JanuviaTM), commonly prescribed to treat type II diabetes -- providing a targeted weapon that can potentially slow, halt, or even prevent tumor growth. This project will develop a therapeutic regime using Sitagliptin, in combination with standard chemotherapy, as a novel approach to the treatment of ovarian cancer. This study directly addresses the Ovarian Cancer Research Program Area of Encouragement "Optimizing Immunotherapies." New approaches for the treatment of ovarian cancer are urgently needed to combat the very high mortality rate for women diagnosed with this disease. This project will develop a novel approach to ovarian cancer treatment, aimed at assisting the body s natural anti-tumor immune defense against tumors. In combination with existing modalities, we believe that developing a strategy using Sitagliptin will substantially improve responses to existing, first-line chemotherapy. Moreover, Sitagliptin has an existing Food and Drug Administration-approved status for the treatment of diabetes, and is proven safe with few side effects. This ensures that the "lead time" for clinical implementation will be rapid. The strategy developed in this project will be easily integrated into existing, standard clinical practices, and hence will be applicable to most patients diagnosed. In addition, the same mechanism is likely to operate in many other solid tumor types; this means that development of a strategy to treat ovarian cancer may prove to be highly relevant to other types of cancers. The outcomes of this study will proceed directly to human trials. Development of new therapies will significantly improve survival for ovarian cancer patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610637
Entities
People
- Magdalena Plebanski
Organizations
- Monash University
- United States Army