Accession Number:

AD1062936

Title:

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

Descriptive Note:

Technical Report,01 Sep 2017,31 Aug 2018

Corporate Author:

University of Texas Southwestern Medical Center Dallas United States

Personal Author(s):

• Hsieh, Jer-Tsong

Report Date:

2018-09-01

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 multidisciplinary 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 ARV7- expressing CRPC in preclinical mouse models.

Descriptors:

• prostate cancer
• epigenetics
• androgens
• genes
• metastasis
• inhibitors
• neoplasms
• cell line
• ribonucleic acids

Subject Categories:

• Medicine and Medical Research
• Biochemistry
• Genetic Engineering and Molecular Biology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE