The Effect of Glycolytic Modulation on Prostate Cancer
Final rept. 25 Oct 2004-30 Jun 2010
UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY NEW BRUNSWICK
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Advanced prostate cancer is only temporarily controlled by androgen ablation therapy or chemotherapy, warranting the study of novel approaches. In this regard, recent studies have demonstrated that abnormal growth factor and apoptotic pathways, required by tumor cells to resist multiple insults, can drive tumor cells to even further dependence on glycolysis, supporting a rationale for selectivity of abrogating glycolysis in tumor cells compared to normal cells. Additional recent studies have demonstrated that starvation of tumor cells may induce the process of autophagy, or cell self digestion, and that autophagy may represent a mechanism of tumor cell resistance if allowed to continue only temporarily, followed by cell death if the process of autophagy continues for a prolonged period. In this proposal, we test the hypothesis that modulation of glycolysis will improve clinical results. We therefore hypothesize that 2-deoxyglucose will be safe and active in patients, and abnormal cell pathways such as constitutive activation of Akt, abnormal regulation of autophagy, and other oncogenes may increase sensitivity to inhibition of glycolysis. To test this hypothesis we have the following specific aims 1. 1. To inhibit glycolysis in patients with prostate cancer in a phase III study of 2-deoxyglucose. 2. 2. To determine the mechanism of inhibition of tumor cell growth through modulation of glycolysis.
- Medicine and Medical Research