Validation and Interrogation of Differentially Expressed and Alternately Spliced Genes in African American Prostate Cancer
Abstract
We have discovered RNA splicing as a novel mechanism underlying tumor aggressiveness and drug resistance in African American (AA) prostate cancer (PCa). To interrogate further the contribution of RNA splicing to the more aggressive PCa biology in AA men, we are collecting AA and white PCa patient blood and tissue specimens of varying Gleason grade for study. In addition, we have identified RNA splicing regulatory variants that associate with PCa risk, aggressiveness and/or survival. Furthermore, we have developed a splice-switching oligonucleotide (SSO) that inhibits production of a pathogenic androgen receptor (AR) variant at the RNA- and protein-level, while maintaining expression of full-length AR, which has therapeutic value. This SSO inhibits proliferation of PCa cells and restores sensitivity to an AR inhibitor. In addition, we have developed SSOs that drive production of inhibitory dominant-negative epidermal growth factor receptor (EGFR) isoforms at the RNA-level and decrease phosphorylated EGFR protein. Ultimately, this study will establish novel biological differences between AA and white PCa and their relevance to tumor biology, which will aid in the development of new biomarkers and/or therapeutics that will reduce PCa health disparities for AAs and improve outcomes for men of all races with aggressive disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2017
- Accession Number
- AD1043095
Entities
People
- Steven R. Patierno
Organizations
- Duke University