Imaging Prostate Cancer (PCa) Phenotype and Evolution
Technical Report,30 Sep 2015,29 Sep 2016
Memorlal Sloan Kettering Institute for Cancer Research New York United States
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The goal of the project is to investigate the potential of inhibiting iron metabolism to inhibit prostate cancer growth.Specifically, we will study Deferiprone, an iron chelator, and focus on its effect on aconitase in prostate tumors. It has been shown that changes in citrate metabolism at the level of mitochondrial aconitase, is an early change in carcinogenesis in the prostate. This change in metabolism is detectable by magnetic resonance. The project includes both in vitro and in vivo studies to determine its potential utility for clinical translation. Our findings to date include that deferiprone in 4 cell lines has an IC50 inhibitory concentration for 50 of cells of about 50uM typical serum levels after standard dose 100uM, inhibits tumor growth in vivo in 2 transgenic prostate tumor models. We have had difficulty with monitoring in vivo glucose metabolism and thus switched to using iron imaging as a non-invasive surrogate for monitoring DFP activity. In year 3 we have completed development of aconitase knockdown cell lines to test the hypothesis that DFPs iron chelating activity decreases activity and expression of aconitase. Our results show a significant effect on tumor doubling time but more modest than deferiprone. In the knockdown cells, DFP has only a modest effect as expected.
- Medicine and Medical Research