ERG induces taxane resistance in castration-resistant prostate cancer

• DOI: 10.1038/ncomms6548
• Publication Date: 2014-11-25T11:54:56Z
• Authors: Giuseppe Galletti; Alexandre Matov; Himisha Beltran; Jacqueline Fontugne; Juan Miguel Mosquera; Cynthia Cheung; Theresa Y. MacDonald; Matthew Sung; Sandra O’Toole; James G. Kench; Sung Suk Chae; Dragi Kimovski; Scott T. Tagawa; David M. Nanus; Mark A. Rubin; Lisa G. Horvath; Paraskevi Giannak...; David S. Rickman
• Keywords: Cabazitaxel; Taxane; Erg

Taxanes are the only chemotherapies used to treat patients with metastatic castration-resistant prostate cancer (CRPC). Despite initial efficacy of taxanes in treating CRPC, all ultimately fail due development drug resistance. In this study, we show that ERG overexpression vitro and vivo models CRPC is associated decreased sensitivity taxanes. affects several parameters microtubule dynamics inhibits effective drug-target engagement docetaxel or cabazitaxel tubulin. Finally, analysis a cohort 34 men treated chemotherapy reveals ERG-overexpressing cancers have twice chance resistance than ERG-negative cancers. Our data suggest plays role beyond regulating gene expression functions outside nucleus cooperate tubulin towards taxane insensitivity. Determining rearrangement status may aid patient selection for therapy and/or influence co-targeting approaches.