Validation and Interrogation of Differentially Expressed and Alternately Spliced Genes in African American Prostate Cancer
Technical Report,30 Sep 2016,29 Sep 2017
Duke University Durham United States
Pagination or Media Count:
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 andor 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 andor therapeutics that will reduce PCa health disparities for AAs and improve outcomes for men of all races with aggressive disease.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology