Skip to main content
SpringerLink
Log in

Spleißvariante AR-V7

Ist die Zeit reif für ihre routinemäßige Anwendung als prädiktiver Marker beim Prostatakarzinom?

Splice variant AR-V7

Is it time for its routine use as a predictive marker in prostate cancer?

  • Molekulare Urologie praxisnah
  • Published:
Der Urologe Aims and scope Submit manuscript

Zusammenfassung

Androgenrezeptorspleißvarianten weisen im Gegensatz zum normalen Androgenrezeptor keine funktionsfähige Ligandenbindungsdomäne auf und tragen damit zur Entwicklung eines metastasierten kastrationsresistenten Prostatakarzinoms bei, das pharmakologisch nicht mehr durch Androgenrezeptorsignalinhibitoren, wie Abirateron oder Enzalutamid, therapierbar ist. Insbesondere die AR-V7 wurde kürzlich als potenzieller prädiktiver Biomarker für Patienten identifiziert, die eher von einer Chemotherapie mit Taxanen profitieren könnten. Viele Studien beschäftigen sich aktuell mit der Relevanz der AR-V7 und beschreiben verschiedene Methoden zum Nachweis der AR-V7-Expression. Dabei ist der klinische Nutzen der AR-V7 zunächst noch mit Vorsicht zu bewerten. Mit diesem Kurzreview möchten die Autoren die aktuelle Evidenz rund um die AR-V7 beleuchten und mögliche Schlussfolgerungen für die Praxis diskutieren.

Abstract

Androgen receptor splice variants (AR-Vs), if overexpressed, lack the ligand-binding domain conveying metastasized castration-resistant prostate cancer with a therapeutic resistance to androgen receptor signaling inhibitors. Particularly AR-V7 has recently been proposed as a potential predictive biomarker to identify patients who would probably benefit most from taxane-based cytotoxic treatment. Several assays to substantiate or quantify AR-V7 expression have recently been proposed. However, their broad clinical value is still debatable. This contemporary update aims to shed light on the current evidence in the field and draw distinct practical conclusions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1

Literatur

  1. Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC et al (2014) AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N Engl J Med 371:1028–1038

    Article  PubMed  PubMed Central  Google Scholar 

  2. Antonarakis ES, Lu C, Luber B, Wang H, Chen Y, Nakazawa M et al (2015) Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncol 1:582–591

    Article  PubMed  PubMed Central  Google Scholar 

  3. Scher HI, Graf RP, Schreiber NA, McLaughlin B, Lu D, Louw J et al (2016) Nuclear-specific AR-V7 protein localization is necessary to guide treatment selection in metastatic castration-resistant prostate cancer. Eur Urol. doi:10.1016/j.eururo.2016.11.024

    Google Scholar 

  4. Scher HI, Lu D, Schreiber NA, Louw J, Graf RP, Vargas HA et al (2016) Association of AR-V7 on circulating tumor cells as a treatment-specific Biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncol 2:1441–1449

    Article  PubMed  PubMed Central  Google Scholar 

  5. Qu F, Xie W, Nakabayashi M, Zhang H, Jeong SH, Wang X et al (2017) Association of AR-V7 and prostate-specific antigen RNA levels in blood with efficacy of abiraterone acetate and enzalutamide treatment in men with prostate cancer. Clin. Cancer Res 23:726–734

    CAS  Google Scholar 

  6. Todenhofer T, Azad A, Stewart C, Gao J, Eigl BJ, Gleave ME et al (2017) AR-V7 transcripts in whole blood RNA of patients with metastatic castration resistant prostate cancer correlate with response to abiraterone acetate. J Urol 197:135–142

    Article  CAS  PubMed  Google Scholar 

  7. Del Re M, Biasco E, Crucitta S, Derosa L, Rofi E, Orlandini C et al (2017) The detection of androgen receptor splice variant 7 in plasma-derived exosomal RNA strongly predicts resistance to hormonal therapy in metastatic prostate cancer patients. Eur Urol 71:680–687

    Article  PubMed  Google Scholar 

  8. Takeuchi T, Okuno Y, Hattori-Kato M, Zaitsu M, Mikami K (2016) Detection of AR-V7 mRNA in whole blood may not predict the effectiveness of novel endocrine drugs for castration-resistant prostate cancer. Res Rep Urol 8:21–25

    PubMed  PubMed Central  Google Scholar 

  9. Miyamoto DT, Zheng Y, Wittner BS, Lee RJ, Zhu H, Broderick KT et al (2015) RNA-Seq of single prostate CTCs implicates noncanonical Wnt signaling in antiandrogen resistance. Science 349:1351–1356

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bernemann C, Schnoeller TJ, Luedeke M, Steinestel K, Boegemann M, Schrader AJ et al (2017) Expression of AR-V7 in circulating tumour cells does not preclude response to next generation androgen deprivation therapy in patients with castration resistant prostate cancer. Eur Urol 71:1–3

    Article  CAS  PubMed  Google Scholar 

  11. Steinestel J, Luedeke M, Arndt A, Schnoeller TJ, Lennerz JK, Wurm C et al (2015) Detecting predictive androgen receptor modifications in circulating prostate cancer cells. Oncotarget. doi:10.18632/oncotarget.3925

    PubMed  PubMed Central  Google Scholar 

  12. Badrising SK, van der Noort V, van den Eertwegh AJ, Hamberg P, van Oort IM, van den Berg HP et al (2016) Prognostic parameters for response to enzalutamide after docetaxel and abiraterone treatment in metastatic castration-resistant prostate cancer patients; a possible time relation. Prostate 76:32–40

    Article  CAS  PubMed  Google Scholar 

  13. Antonarakis ES, Lu C, Luber B, Wang H, Chen Y, Zhu Y et al (2017) Clinical significance of androgen receptor splice variant-7 mRNA detection in circulating tumor cells of men with metastatic castration-resistant prostate cancer treated with first- and second-line Abiraterone and Enzalutamide. J Clin Oncol. doi:10.1200/JCO.2016.70.1961.JCO2016701961

    Google Scholar 

  14. Antonarakis ES, Chandhasin C, Osbourne E, Luo J, Sadar MD, Perabo F (2016) Targeting the N‑terminal domain of the androgen receptor: a new approach for the treatment of advanced prostate cancer. Oncologist 21:1427–1435

    Article  PubMed  PubMed Central  Google Scholar 

  15. Liu C, Armstrong C, Zhu Y, Lou W, Gao AC (2016) Niclosamide enhances abiraterone treatment via inhibition of androgen receptor variants in castration resistant prostate cancer. Oncotarget 7:32210–32220

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gehrig J, Kaulfuss S, Jarry H, Bremmer F, Stettner M, Burfeind P et al (2017) Prospects of estrogen receptor beta activation in the treatment of castration-resistant prostate cancer. Oncotarget. doi:10.18632/oncotarget.16496

    PubMed  PubMed Central  Google Scholar 

  17. Schweizer MT, Antonarakis ES, Denmeade SR (2017) Bipolar androgen therapy: a paradoxical approach for the treatment of castration-resistant prostate cancer. Eur Urol. doi:10.1016/j.eururo.2017.03.022

    PubMed  Google Scholar 

  18. Schweizer MT, Wang H, Luber B, Nadal R, Spitz A, Rosen DM et al (2016) Bipolar androgen therapy for men with androgen ablation naive prostate cancer: results from the Phase II BATMAN Study. Prostate 76:1218–1226

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Urologie und Kinderurologie, Universitätsmedizin Mainz, Mainz, Deutschland

    I. Tsaur

  2. Forschungskoordination, Deutsche Gesellschaft für Urologie e. V., Uerdinger Straße 64, 40474, Düsseldorf, Deutschland

    C. Becker

  3. Klinik für Urologie, Universitätsmedizin Göttingen, Göttingen, Deutschland

    P. Thelen

  4. Klinik für Urologie und Kinderurologie des Universitätsklinikums der Johann Wolfgang Goethe Universität Frankfurt, Frankfurt, Deutschland

    F. C. Roos

  5. Fachgruppe Molekulare Urologie der Arbeitsgruppe urologische Forschung der Deutschen Gesellschaft für Urologie, Düsseldorf, Deutschland

    I. Tsaur

Authors
  1. I. Tsaur
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Thelen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. C. Roos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Becker.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsaur, I., Becker, C., Thelen, P. et al. Spleißvariante AR-V7. Urologe 56, 1164–1167 (2017). https://doi.org/10.1007/s00120-017-0461-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00120-017-0461-x

Schlüsselwörter

Keywords

Search

Navigation