title: Androgen receptor variation affects prostate cancer progression and drug resistance.
abstract: Significant therapeutic progress has been made in treating prostate cancer in recent years. Drugs such as enzalutamide, abiraterone, and cabazitaxel have expanded the treatment armamentarium, although it is not completely clear which of these drugs are the most-effective option for individual patients. Moreover, such advances have been tempered by the development of therapeutic resistance. The purpose of this review is to summarize the current literature pertaining to the biochemical effects of AR variants and their consequences on prostate cancer therapies at both the molecular level and in clinical treatment. We address how these AR splice variants and mutations affect tumor progression and therapeutic resistance and discuss potential novel therapeutic strategies under development. It is hoped that these therapies can be administered with increasing precision as tumor genotyping methods become more sophisticated, thereby lending clinicians a better understanding of the underlying biology of prostate tumors in individual patients.
authors.affiliation: Molecular Pharmacology Section, Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, United States.
authors.forename: Edel
authors.initials: E
authors.lastname: McCrea
authors.affiliation: The Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, United States.
authors.forename: Tristan M
authors.initials: TM
authors.lastname: Sissung
authors.affiliation: Molecular Pharmacology Section, Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, United States.
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Price
authors.affiliation: Molecular Pharmacology Section, Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, United States.
authors.forename: Cindy H
authors.initials: CH
authors.lastname: Chau
authors.affiliation: Molecular Pharmacology Section, Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, United States; The Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD, United States. Electronic address: wdfigg@helix.nih.gov.
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics*
chemical_list: C410798:AR protein, human; D000970:Antineoplastic Agents; D011944:Receptors, Androgen
keywords: AR-V7; Androgen receptor; Mutation; Pharmacology; Prostate cancer