Open AccessCombination therapy with androgen receptor N‐terminal domain antagonist EPI‐7170 and enzalutamide yields synergistic activity in AR‐V7‐positive prostate cancer
Author(s) -
Hirayama Yukiyoshi,
Tam Teresa,
Jian Kunzhong,
Andersen Raymond J.,
Sadar Marianne D.
Publication year - 2020
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12770
Subject(s) - enzalutamide , androgen receptor , prostate cancer , cancer research , pharmacology , chemistry , cancer , medicine
Ralaniten and analogs (EPI) bind androgen receptor N‐terminal domain (AR‐NTD) to block the transcriptional activities of full‐length AR (FL‐AR) and AR splice variants (AR‐Vs). Enzalutamide (ENZ) elevates levels of AR‐V7 leading to resistance and increased proliferation. Targeting AR‐NTD to block FL‐AR and AR‐Vs with EPI in combination with ENZ resulted in synergistic inhibition of proliferation of ENZ‐resistant prostate cancer cells.