Accession Number : AD1043095


Title :   Validation and Interrogation of Differentially Expressed and Alternately Spliced Genes in African American Prostate Cancer


Descriptive Note : Technical Report,30 Sep 2016,29 Sep 2017


Corporate Author : Duke University Durham United States


Personal Author(s) : Patierno, Steven


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1043095.pdf


Report Date : 01 Oct 2017


Pagination or Media Count : 24


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.


Descriptors :   Prostate cancer , gene expression , neoplasms , African americans , ribonucleic acids , Caucasians , NUCLEOTIDES , inhibitors , androgens , biological markers


Subject Categories : Medicine and Medical Research
      Genetic Engineering and Molecular Biology
      Biochemistry


Distribution Statement : APPROVED FOR PUBLIC RELEASE