Accession Number : AD1050379


Title :   Epigenetic Machinery Regulates Alternative Splicing of Androgen Receptor (AR) Gene in Castration Resistant Prostate Cancer


Descriptive Note : Technical Report,01 Sep 2016,31 Aug 2017


Corporate Author : UT Southwestern Medical Center Dallas United States


Personal Author(s) : Liu, Zhi-Ping


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1050379.pdf


Report Date : 01 Sep 2017


Pagination or Media Count : 13


Abstract : Androgen deprivation therapy (ADT) is the primary treatment for metastatic prostate cancer (PCa) since PCa depends on androgen for growth. Although initially responsive, most tumors progress into androgen-independent/castration-resistant PCa (CRPC). No curative therapy is available. One of the reasons for the resistance to ADT and newer anti-androgen drugs is the emergence of constitutively active AR variants (AR-Vs) such as AR-V7 that are induced under ADT conditions. Our research goal is to test the hypothesis that the epigenetic regulator KDM4B, a histone lysine demethylase, promotes AR-V7 via alternative splicing, leading to CPRC. A multi-disciplinary approach including molecular biology, tumor biology, cell biology, and biochemical method is used to test this hypothesis. In collaboration with a partnering principal investigator we are also testing the efficacy of our newly identified KDM4B inhibitor(s) as a monotherapy or combined with approved anti-androgen agents in AR-V7-expressing CRPC in preclinical mouse models.


Descriptors :   antibodies , culture techniques , drug resistance , biomedical research , proteins , therapy , prostate , androgens , neoplasms , inhibitors , prostate cancer , cell line , castration


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE