Targeting Glutaminase Isoforms for Therapy-Resistant Prostate Cancer
Abstract
Our preliminary study demonstrates that advanced prostate cancer is addicted to glutamine, and a glutaminase isoform switch contributes to the development of therapy resistance and disease progression. The major goal of the project was to study the molecular mechanisms of GLS1 isoform switch and explore the possibility of targeting glutamine metabolism as a novel therapeutic approach. In addition to the achievements reached in Year 1 and Year 2, this year, we have made the following Key Research Accomplishments: 1. We have demonstrated a potential mechanism how c-Myc and N-Myc up-regulate GAC expression. 2. We have demonstrated a dramatic phenotype that advanced PCa cells consume more glutamine utilization. 3. We have demonstrated that the GLS1 selective inhibitor, CB-839, preferentially inhibits tumor growth of advanced PCa cells where GAC predominates. Thus, GLS1/GAC could be an ideal therapeutic target for patients who have run out of treatment of choice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2023
- Accession Number
- AD1196913
Entities
People
- Jiaoti Huang
Organizations
- Duke University