title: Androgen Receptor Rearrangement and Splicing Variants in Resistance to Endocrine Therapies in Prostate Cancer.
abstract: In the last few years, the survival of patients with castration-resistant prostate cancer (CRPC) has significantly improved as a result of the development of second-generation androgen deprivation therapies such as abiraterone and second-generation antagonists such as enzalutamide. However, CRPC patients rapidly develop resistance to these drugs, in many cases because of reactivation of the therapeutic target, the androgen receptor (AR) transcription factor. Several mechanisms responsible for AR transcriptional reactivation have been demonstrated, including mutation, amplification, and rearrangement of the AR gene, transcriptional compensation by alternative steroid receptors, and mutation or copy number alteration of genes encoding AR coregulators. In addition, CRPC tumors display elevated expression of truncated AR variants (AR-Vs) that can arise from alternative splicing or underlying AR gene rearrangements. In this review, we discuss general mechanisms of resistance to androgen/AR-targeted therapies, with a focus on the role of AR-Vs in conferring resistance to abiraterone or enzalutamide in CRPC patients.
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Yeung
authors.initials: Y
authors.lastname: Ho
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455.|Departments of Laboratory Medicine and Pathology and Urology, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Dehm
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen