Epigenetic Machinery Regulates Alternative Splicing of Androgen Receptor (AR) Gene in Castration-Resistant Prostate Cancer (CRPC)
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2020
- Accession Number
- AD1129206
Entities
People
- Jer-Tsong Hsieh
Organizations
- University of Texas Southwestern Medical Center