Inhibition of Glycolysis for NEPC Treatment
Abstract
Prostate cancers in the late-stage after androgen depravation therapy plus anti-androgen treatment with XtandiR (a.k.a. Enzalutamide or MDV3100) or ZytigaR. (a.k.a. Abiraterone) often become a neuronal tissue-like malignancy, which is lethal without any clinical treatment. Recent studies from our group and others revealed that this subtype of prostate cancers with neuronal tissue-like feature (termed as treatment-induced NEPC or t-NEPC) exert high levels of glucose usage due to multiple alterations of glycolytic enzyme modification. Our preliminary studies identified a key enzyme, Glyceraldehyde-3-Phosphate Dehydrogenase (abbreviated as GAPDH), as a critical player in the t-NEPC phenotype development. In this project, we will expand our investigation into multiple prostate cancer cell lines and patient-derived tissues in frozen condition or implanted in animals. We will confirm GAPDH’s role in promoting the t-NEPC phenotype development. We will examine the therapeutic efficacy of a novel small chemical compound Alternol that we have worked on for the last 5 years in disrupting the t-NEPC phenotype development in several clinically relevant animal models that recapitulate the clinical t-NEPC phenotype. Overarching Challenges: This project addresses two of the FY19 PCRP Overarching Challenges: “define the biology of lethal prostate cancer to reduce death” and “develop treatments that improve outcomes for men with lethal prostate cancer.” Successful completion will provide a huge benefit for late-stage prostate cancer patients after ADT and anti-androgen treatment who develop treatment resistance. The novel therapy with Alternol or any other GAPDH-specific inhibitors will provide new hopes for patients who developed anti-androgen drug resistance. Although these new drugs might have certain under-defined toxicity as any other therapeutic drugs, our next plan will formulate a prostate cancer-specific delivery approach to minimize the systemic side effects that the new therapy might have. This is a translational study with near future implication in the clinic.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010637
Entities
People
- Benyi Li
Organizations
- United States Army
- University of Kansas Medical Center