A Novel Prodrug Strategy to Treat Prostate Cancer by Targeting MYC-Driven Nucleotide Biosynthesis
Abstract
Although several new drugs have been recently approved for the treatment of castration-resistant prostate cancer (CRPC), the responses in patients typically last for about 16 months. Complicating the matter even further, recent evidence has suggested that there is a rising incidence of small cell prostate cancer in treatment-resistant CRPC, suggesting the disease may be evolving to escape targets expressed only in the more common adenocarcinoma form. On this basis, there is an urgent need to identify new targets and therapeutic approaches to cure this disease. Recent data have shown that the protein MYC is a dominant driver of both adenocarcinoma and small cell prostate cancer. We have also discovered an actionable downstream target of MYC, and the purpose of this proposal is to develop a new radiolabeled molecule that will engage this target to selectively accumulate in tumor cells with hyperactive MYC. This therapy is most relevant to patients with CRPC, although it also may have relevance to treating oligometastatic disease as MYC is involved in early-stage prostate cancer. Because small molecule therapies are more straightforward to translate that biologic-based therapies, we can reasonably project Investigational New Drug (IND)-enabling studies within 5 years of the completion of this project. Overall, this project is innovative and impactful because it outlines an entirely new strategy to induce cancer cell death by targeting one of most dominant drivers of early and late-stage prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710198
Entities
People
- Matthew Parker
Organizations
- United States Army
- University of California, San Francisco