Efficacy of Lysine-Specific Demethylase 1 Inhibition in PCa
Abstract
Lysine Specific Demethylase 1 (LSD1, KDM1A) has been characterized as an enzyme that removes methyl groups from histones and thereby turns off the expression of the associated genes. Many of these genes that are turned off in advanced prostate cancer (PCa) may be involved in suppressing cell growth and stimulated cell differentiation, so that by repressing these genes LSD1 is stimulating tumor growth. Significantly, LSD1 is also associated with the androgen receptor (AR) and is needed by AR to stimulate gene expression. Based on these properties, we hypothesize that treatment with an LSD1 inhibitor will be efficacious in PCa as it will both turn back on genes that repress growth and block the activities of AR that stimulate tumor growth. Our overall objective in this proposal is to test these hypotheses by examining the effects of LSD1 inhibition in PCa cell line and mouse xenograft models. Significantly, potent and specific LSD1 inhibitors are being developed and entering phase 1 trials as epigenetic modifiers for leukemia. Therefore, if successful, the results of this study could be rapidly translated into clinical trials for men with advanced PCa, including castration-resistant PCa.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510135
Entities
People
- Steven P Balk
Organizations
- Beth Israel Deaconess Medical Center
- United States Army