Brian Winters1, Lisha Brown1, Ilsa Coleman2, Holly Nguyen1, Tsion Zewdu Minas3, Lori Kollath1, Valeri Vasioukhin2, Peter Nelson2, Eva Corey1, Aykut Üren3, Colm Morrissey4. 1. Department of Urology, University of Washington, Seattle, WA, U.S.A. 2. Fred Hutchinson Cancer Research Center, Seattle, WA, U.S.A. 3. Department of Oncology Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, DC, U.S.A. 4. Department of Urology, University of Washington, Seattle, WA, U.S.A. cmorriss@uw.edu.
Abstract
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. Copyright
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 cancerpatient-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. Copyright
Authors: Christopher M Schafer; Jami M Gurley; Katarzyna Kurylowicz; Prisca K Lin; Wen Chen; Michael H Elliott; George E Davis; Faizah Bhatti; Courtney T Griffin Journal: Proc Natl Acad Sci U S A Date: 2020-10-05 Impact factor: 11.205
Authors: Sean Porazinski; Michael Ladomery; Ling Li; Lisa Hobson; Laura Perry; Bethany Clark; Susan Heavey; Aiman Haider; Ashwin Sridhar; Greg Shaw; John Kelly; Alex Freeman; Ian Wilson; Hayley Whitaker; Elmar Nurmemmedov; Sebastian Oltean Journal: Br J Cancer Date: 2020-06-25 Impact factor: 7.640
Authors: Juha Mehtonen; Susanna Teppo; Mari Lahnalampi; Aleksi Kokko; Riina Kaukonen; Laura Oksa; Maria Bouvy-Liivrand; Alena Malyukova; Artturi Mäkinen; Saara Laukkanen; Petri I Mäkinen; Samuli Rounioja; Pekka Ruusuvuori; Olle Sangfelt; Riikka Lund; Tapio Lönnberg; Olli Lohi; Merja Heinäniemi Journal: Genome Med Date: 2020-11-20 Impact factor: 11.117