DID YOU KNOW? DTIC has over 3.5 million final reports on DoD funded research, development, test, and evaluation activities available to our registered users. Click HERE
to register or log in.
Preclinical and Clinical Investigation of the Impact of Obesity on Ovarian Cancer Pathogenesis
Annual rept. 25 Sep 2013-24 Sep 2014
NORTH CAROLINA UNIV AT CHAPEL HILL
Pagination or Media Count:
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 metforrnin. We demonstrate 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. Alterations in gene expression were found with elevated BMI in human serous OC tumors in The Cancer Genome Atlas TCGA database. Many of these genes were related to lipid metabolism, specifically apolipoproteins. Metformin but not everolimus was more efficacious in the inhibition of tumor growth in obese versus non-obese mice. For our in vitro studies, metformin and everolimus had similar effects on proliferation, inhibition of mTOR signaling and glycolysis but opposite effects on glucose uptake, which may contribute to metforrnins enhanced anti-tumorigenic effects in the setting of obesity.
APPROVED FOR PUBLIC RELEASE