PT  - JOURNAL ARTICLE
AU  - BRIAN WINTERS
AU  - LISHA BROWN
AU  - ILSA COLEMAN
AU  - HOLLY NGUYEN
AU  - TSION ZEWDU MINAS
AU  - LORI KOLLATH
AU  - VALERI VASIOUKHIN
AU  - PETER NELSON
AU  - EVA COREY
AU  - AYKUT ÜREN
AU  - COLM MORRISSEY
TI  - Inhibition of ERG Activity in Patient-derived Prostate Cancer Xenografts by YK-4-279
DP  - 2017 Jul 01
TA  - Anticancer Research
PG  - 3385--3396
VI  - 37
IP  - 7
4099  - http://ar.iiarjournals.org/content/37/7/3385.short
4100  - http://ar.iiarjournals.org/content/37/7/3385.full
SO  - Anticancer Res2017 Jul 01; 37
AB  - Background/Aim: The aim of the current study was to determine the effects of the ERG small-molecule inhibitor YK-4-279 on ERG+ prostate cancer patient-derived xenografts (PDX). Materials and Methods: ERG activity was blocked using YK-4-279 in three subcutaneously-implanted ERG+ (LuCaP 23.1, 86.2 and 35) and one ERG− (LuCaP 96) PDX. Treated animals tumor volume (TV), body weight (BW) and serum prostate-specific antigen (PSA) were compared to vehicle-treated control animals. Gene expression, proliferation, apoptosis, microvessel density and ERG expression were also assessed. Results: Administration of YK-4-279 decreased TV (p=0.026), proliferation (p=0.0038) and PSA (p=0.022) in Severe Combined Immunodeficiency (SCID) mice bearing LuCaP 23.1 tumors. LuCaP 86.2, LuCaP 35 and LuCaP 96 showed no significant changes in TV, or PSA. Mineralocorticoid receptor (MR) and MR-direct target genes were up-regulated in treatment-resistant LuCaP 86.2 and LuCaP 35 PDX. Conclusion: YK-4-279 decreased ERG+ LuCaP 23.1 tumor growth, but not LuCaP 86.2 and LuCaP 35 ERG+ tumor growth.