Inhibition of ERG Activity in Patient-derived Prostate Cancer Xenografts by YK-4-279

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.

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