Pre-clinical and Clinical Investigation of the Impact of Obesity on Ovarian Cancer Pathogenesis
Abstract
The metabolic consequences of obesity may be critical in the development of ovarian cancer (OC), resulting in biologically different cancers than those that arise in leaner women. This may occur through aberrant modulation of mTOR signaling, given that alterations in this pathway are common in both obesity and OC. Thus, obese OC patients may derive increased benefit from chemotherapeutic agents related to inhibition of this pathway, such as mTOR inhibitors (everolimus) or metformin. We have demonstrated that the obese state can promote tumor progression in the KpB mouse model of OC. The ovarian tumors that arose in the obese mice were genomically and metabolically different from those that arose in non-obese mice. Metformin was found to be more efficacious in the obese versus non-obese KpB mice, suggesting that obesity may be a biomarker for response to this agent. For our in vitro studies, metformin and everolimus were found to be more effective in the inhibition of proliferation and induction of apoptosis under low versus high glucose concentrations. We postulate that OC cells deprived of glucose have blunted proliferative capacity, rendering them more susceptible to metformin and everolimus, and that a high glucose environment may overall enhance proliferative capacity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA598205
Entities
People
- Victoria Bae-jump
Organizations
- University of North Carolina at Chapel Hill