title: Serial blood-based analysis of AR-V7 in men with advanced prostate cancer.
abstract: BACKGROUND
  We previously showed that pretreatment detection of androgen receptor splice variant-7 (AR-V7) in circulating tumor cells (CTCs) from men with castration-resistant prostate cancer is associated with resistance to abiraterone and enzalutamide, but not to taxane chemotherapies. Here, we conducted serial measurements of AR-V7 and evaluated patterns of longitudinal AR-V7 dynamics over the course of multiple sequential therapies.
  
  
  METHODS
  Metastatic prostate cancer patients treated at Johns Hopkins with AR-directed therapies or taxane chemotherapies underwent serial liquid biopsies for CTC-based AR-V7 analysis at baseline, during therapy, and at progression. We used a CTC enrichment platform followed by multiplexed reverse-transcription polymerase chain reaction analysis to detect full-length androgen receptor and AR-V7 transcripts. Patients selected for inclusion in this report were those who provided ≥4 CTC samples, at least one of which was AR-V7 positive, over the course of ≥2 consecutive therapies.
  
  
  RESULTS
  We identified 14 patients who received a total of 37 therapies and contributed 70 CTC samples for AR-V7 analysis during a median follow-up period of 11 months. Three patients remained AR-V7 positive during the entire course of therapy. The remainder underwent transitions in AR-V7 status: there were eight instances of 'conversions' from AR-V7-negative to -positive status (during treatment with first-line androgen deprivation therapy, abiraterone, enzalutamide, and docetaxel), and six instances of 'reversions' from AR-V7-positive to -negative status (during treatment with docetaxel and cabazitaxel).
  
  
  CONCLUSIONS
  AR-V7 is a dynamic marker, and transitions in AR-V7 status may reflect selective pressures on the tumor exerted by therapeutic interventions. While 'conversions' to AR-V7-positive status were observed with both AR-directed therapies and taxane chemotherapies, 'reversions' to AR-V7-negative status only occurred during taxane therapies. Serial blood-based AR-V7 testing is feasible in routine clinical practice, and may provide insights into temporal changes in tumor evolution.
authors.affiliation: Department of Urology, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nakazawa
authors.affiliation: Department of Urology, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Urology, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Paller
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Carducci
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Eisenberger
authors.affiliation: Department of Urology, Johns Hopkins University School of Medicine, Baltimore, USA. Electronic address: jluo1@jhmi.edu.
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Antonarakis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: C410798:AR protein, human; D000736:Androstenes; D000970:Antineoplastic Agents; D001549:Benzamides; D014408:Biomarkers, Tumor; D009570:Nitriles; D020033:Protein Isoforms; D011944:Receptors, Androgen; D043823:Taxoids; D000077143:Docetaxel; D010669:Phenylthiohydantoin; C552428:cabazitaxel; C540278:enzalutamide; C089740:abiraterone
keywords: AR-V7; androgen receptor; circulating tumor cell; prostate cancer; splice variant