Accession Number:

AD1062942

Title:

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

Descriptive Note:

Technical Report,01 Sep 2017,31 Aug 2018

Corporate Author:

UT Southwestern Medical Center Dallas United States

Personal Author(s):

• Liu, Zhi-Ping

Report Date:

2018-09-01

Pagination or Media Count:

10.0

Abstract:

Androgen receptor pathway inhibition ARPI 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 ways for PCa cell to evade targeted therapy is the emergence of constitutively active AR variants AR-Vs such as AR-V7 that does not depend on androgen. 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. We have made significant progress in the last year on identification of the mechanism by which KDM4B regulates AR-V7 and establishing the efficacy of our newly identified KDM4B inhibitor B3 as a monotherapy or combined with approved anti-androgen agents in AR-V7-expressing CRPC in preclinical mouse models.

Descriptors:

• epigenetics
• androgens
• genes
• prostate cancer
• neoplasms
• inhibition
• metastasis
• inhibitors
• ribonucleic acids

Subject Categories:

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

Distribution Statement:

APPROVED FOR PUBLIC RELEASE