Accession Number:

AD1095811

Title:

Epigenetic Machinery Regulates Alternative Splicing of Androgen Receptor Gene in Castration-Resistant Prostate Cancer

Descriptive Note:

Technical Report,01 Sep 2018,31 Aug 2019

Corporate Author:

UT Southwestern Medical Center Dallas United States

Personal Author(s):

Report Date:

2019-09-01

Pagination or Media Count:

8.0

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 independentcastration-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 ARV7 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 inhibitors as a monotherapy or combined with approved anti-androgen agents in AR-V7expressing CRPC in preclinical mouse models.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE