Exploiting a Novel Vulnerability in Prostate Cancer
Abstract
Current treatments for prostate cancer that are based on inhibition of androgen receptor (AR) signaling are generally not durable, owing to the ability of cancer cells to acquire molecular changes that promote drug resistance. Molecular changes in castrate-resistant prostate cancer (CRPC) include mutations and altered RNA splicing that give rise to therapy-resistant forms of AR. We have devised a novel strategy for inhibiting prostate cancer cells. The strategy uses a new drug that has yielded promising results in preclinical models of lung cancer. The strategy involves induced expression of the drug target, which is an enzyme with known biological functions. The drug-enzyme complex induces cell growth inhibition in multiple prostate cancer models through a mechanism referred to as a dominant-negative effect. The growth inhibition is observed in AR-positive, AR-negative, and AR-mutant prostate cancer models. Thus, the strategy has the potential to be effective in therapy-resistant prostate cancer. The strategy includes packaging both the inducer and the drug in nanoparticles (NPs), a tiny carrier that protects the drug from degradation. The NPs are also endowed with a prostate cancer cell- specific targeting signal. This will enable the NPs to bind to prostate cancer cells, deliver its payload of inducer and drug, and inhibit cell growth. The Exploration Hypothesis Development Award will support development and optimization of the NP strategy. The project addresses the PCRP Overarching Challenge of developing treatments that improve outcomes for men with lethal prostate cancer. This is a high-risk/high reward, translational project that represents a novel approach to prostate cancer treatment that can help eliminate death from prostate cancer, which will enhance the well-being of Service Members, Veterans, and all the men, women, and their families who are touched by the impact of the disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310063
Entities
People
- Bryce Paschal
Organizations
- United States Army
- University of Virginia