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RamakrishnanS

Research Abstracts Online
January - December 2011

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University of Minnesota Twin Cities
Medical School
Department of Pharmacology

PI: Sundaram Ramakrishnan

Targeting Abnormal Translation Initiation in Ovarian Cancer Cells

Epithelial ovarian cancer is one of the difficult intraperitoneal cancers to treat. The unique microenvironment of the peritoneum and development of resistance to chemotherapy results in the highest rate of death among gynecologic malignancies in the U.S. Despite a good response to the initial therapy with platinum and taxol, the majority of patients will relapse. Recurrent cancers resist chemotherapy by activating survival responses and by increasing the number of tumor initiating cancer stem cells. Cancer stem cells thrive in hypoxic areas (niche) by modulating protein synthesis and metabolism. Furthermore, cap-dependent protein synthesis is activated in patients with aggressive form of ovarian cancers. Therefore, targeting cap-dependent translation is a viable strategy to eliminate cancer stem cells, reverse chemoresistance and thereby prevent recurrence of ovarian cancer. This project’s hypothesis is that antagonists of translational initiation will inhibit tumor angiogenesis, chemosensitize drug resistant cancer cells and prevent ovarian cancer recurrence. These studies will provide critical data on the efficacy of targeting translational initiation on the recurrence of drug-resistant ovarian cancer and identify novel targets for further development.