title: C-terminally truncated constitutively active androgen receptor variants and their biologic and clinical significance in castration-resistant prostate cancer.
abstract: A mechanism allowing castration resistant prostate cancer cells to escape the effects of conventional anti-hormonal treatments is the synthesis of constitutively active, C-terminally truncated androgen receptor (AR)-variants. Lacking the entire or vast parts of the ligand binding domain, the intended target of traditional endocrine therapies, these AR-variants (termed ARΔLBD) are insensitive to all traditional treatments including second generation compounds like abiraterone, enzalutamide or ARN-509. Although ARΔLBD are predominantly products of alternative splicing, they can also be products of nonsense mutations or proteolytic cleavage. In this review, we will discuss the etiology and function of c-terminally truncated AR-variants and their clinical significance as markers/targets for the treatment of castration resistant prostate cancer.
authors.affiliation: Department of Urology, Ulm University Medical School, 89075 Ulm, Germany.
authors.forename: Anca
authors.initials: A
authors.lastname: Azoitei
authors.affiliation: Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany.
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.affiliation: Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Godau
authors.affiliation: Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany.
authors.forename: M Raschid
authors.initials: MR
authors.lastname: Hoda
authors.affiliation: Department of Pediatric Surgery and Pediatric Urology, University Hospital Tübingen, 72076 Tübingen, Germany.
authors.forename: Evi
authors.initials: E
authors.lastname: Schmid
authors.affiliation: Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, 23538 Lübeck, Germany. Electronic address: marcus.cronauer@uksh.de.
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Cronauer
mesh_terms: D017398:Alternative Splicing; D000728:Androgens / Q000378:metabolism; D000736:Androstenes / Q000737:chemistry; D000737:Androstenols / Q000627:therapeutic use; D000818:Animals; D001549:Benzamides; D014408:Biomarkers, Tumor; D018388:Codon, Terminator; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000737:chemistry; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D015398:Signal Transduction; D013867:Thiohydantoins / Q000737:chemistry; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000728:Androgens; D000736:Androstenes; D000737:Androstenols; D001549:Benzamides; D014408:Biomarkers, Tumor; D018388:Codon, Terminator; D009570:Nitriles; C114750:TCF20 protein, human; D013867:Thiohydantoins; D014157:Transcription Factors; C572045:apalutamide; D010669:Phenylthiohydantoin; C540278:enzalutamide; C089740:abiraterone
keywords: Androgen receptor splice variants; Marker; Prostate cancer; Therapies