title: Metastatic castration-resistant prostate cancer: targeting the mechanisms of resistance to abiraterone acetate and enzalutamide.
abstract: Persistent androgen receptor (AR) axis is a functionally important pathway for prostate cancer cells and it is currently regarded as a critical therapeutic target. Although the impressive clinical activity of new hormonal agents, such as the second-generation AR antagonist enzalutamide (formerly MDV3100) and the selective inhibitor of cytochrome P450 17A1 (CYP17A1) abiraterone acetate (AA), in patients with metastatic castration-resistant prostate cancer (mCRPC), innate or acquired resistance invariably arises. To date, emerging hypotheses are different, but the mechanisms of resistance to these drugs have not yet been clarified. The aim of this review is to summarize the main data available on the evaluation of the multiple levels of development of resistance to next-generation AR-directed therapies. Understanding how the AR is activated may have clinical implications in defining which patients will respond to existing therapeutic agents and provide a proof for making novel strategies.
authors.affiliation: a Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Piazzale L.A. Scuro 10, 37124 Verona, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Modena
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciccarese
authors.forename: Emanuela
authors.initials: E
authors.lastname: Fantinel
authors.forename: Davide
authors.initials: D
authors.lastname: Bimbatti
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.forename: Francesco
authors.initials: F
authors.lastname: Massari
mesh_terms: D000069501:Abiraterone Acetate / Q000494:pharmacology / Q000627:therapeutic use*; D059002:Androgen Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology
chemical_list: D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; D000069501:Abiraterone Acetate
keywords: abiraterone acetate; drug resistance; enzalutamide; metastatic castration-resistant prostate cancer; prostate cancer