Precision Targeting of Castration-Resistant Prostate Cancer with a Novel Ferrous Iron-Dependent Therapeutic Delivery and Tumor Imaging Strategy
Abstract
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 Fe(II), 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 Fe(II)-activated form of a potent DNA-alkylator (TRX-CBI), the Fe(II)-activated form of enzalutamide (TRX-ENZ), and a novel Fe(II)-targeted therapeutic radionuclide, 117Lu-TRX. We will also image prostate cancer in diverse animal models using an Fe(II)-activated PET probe(18F-TRX). Our objective is to show that castration resistant prostate cancer can be addressed effectively with these novel Fe(II)-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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1092583
Entities
People
- Davide Ruggero
Organizations
- University of California, San Francisco