Systematic Identification of Genes Required for Expression of Androgen Receptor Splice Variants
Abstract
Gene therapy through genetic engineering provides a great hope for treatment of human diseases including prostate cancer, because genetic alterations including those with as subtle as a single-nucleotide variation often lead to a defective gene or dysfunctional protein. Potentially, gene therapy would be able to correct these mutations. In addition, these genetic engineering tools will help us to better understand mechanisms underlying these genetic changes. Very recently, a new genetic engineering tool has been developed from bacterial Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-Associated System (CAS). Importantly, it has several advantages over the existing ones and one of them is the ability to make a very large number (tenth of thousands) of gene knockouts so that we can screen genes important to prostate cancer. For example, androgen receptor (AR) is well known for its role in prostate cancer progression and castration resistance, and several AR splicing variants have been identified in castration resistant prostate cancer. With this technology, we can answer questions like how prostate cancer becomes castration-resistant after anti-hormone therapy. Furthermore, these genes screened out with this technology may serve biomarkers or therapeutic targets. Therefore, this work will address Prostate Cancer Research Program overarching challenge "Develop effective treatments and address mechanisms of resistance for men with high risk or metastatic prostate cancer" with focus areas of "Mechanisms of Resistance: Understanding primary and acquired resistance to therapy." Importantly, our application is the first one to perform this type of screening in prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510121
Entities
People
- Yin-Yuan Mo
Organizations
- United States Army
- University of Mississippi