Precision Targeting of Castration Resistant Prostate Cancer with a Novel Ferrous Iron-Dependent Therapeutic Delivery and Tumor Imaging Strategy
Technical Report,30 Sep 2018,29 Sep 2019
University of California San Francisco United States
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We propose that mechanistically unrelated anti-cancer therapeutics can be more effectively deployed by administration in a pro-drug form that conditionally releases the therapeutic after chemical reaction with FeII, pools of which are augmented in CRPC cells and in the tumor microenvironment. To test and validate our hypothesis we will synthesize and evaluate in multiple prostate cancer models three novel agents, the FeII-activated form of a potent DNA-alkylator TRX-CBI, the FeII-activated form of enzalutamide TRX-ENZ, and a novel FeII-targeted therapeutic radionuclide, 117Lu-TRX. We will also image prostate cancer in diverse animal models using an FeII-activated PET probe 18F-TRX. Our objective is to show that castration resistant prostate cancer can be addressed effectively with these novel FeII-targeted approach and that response to therapy can be predicted with 18F-TRX. Successful realization of these objectives via the IDA mechanism will greatly enable our long-term goal of identifying a theranostic development candidate that can be progressed toward first-in-human studies.
- Medicine and Medical Research