Review

. 2018 May;73(5):715-723.

doi: 10.1016/j.eururo.2017.11.038. Epub 2017 Dec 16.

Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting

Jun Luo¹, Gerhardt Attard², Steven P Balk³, Charlotte Bevan⁴, Kerry Burnstein⁵, Laura Cato⁶, Artem Cherkasov⁷, Johann S De Bono⁸, Yan Dong⁹, Allen C Gao¹⁰, Martin Gleave⁷, Hannelore Heemers¹¹, Mayuko Kanayama¹², Ralf Kittler¹³, Joshua M Lang¹⁴, Richard J Lee¹⁵, Christopher J Logothetis¹⁶, Robert Matusik¹⁷, Stephen Plymate¹⁸, Charles L Sawyers¹⁹, Luke A Selth²⁰, Howard Soule²¹, Wayne Tilley²⁰, Nancy L Weigel²², Amina Zoubeidi⁷, Scott M Dehm²³, Ganesh V Raj²⁴

Affiliations

¹ Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jluo1@jhmi.edu.
² The Institute of Cancer Research, London, UK.
³ Hematology-Oncology Division, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁴ Department of Surgery & Cancer, Imperial College London, Imperial Centre for Translational & Experimental Medicine (ICTEM), Hammersmith Hospital Campus, London, UK.
⁵ Department of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA.
⁶ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
⁷ Department of Urologic Sciences, University of British Columbia, The Vancouver Prostate Centre, Vancouver, BC, Canada.
⁸ Division of Clinical Studies, The Institute of Cancer Research, London, UK.
⁹ Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
¹⁰ Department of Urology, University of California Davis, Sacramento, CA, USA.
¹¹ Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Urology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Hematology/Medical Oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
¹² Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
¹³ McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX, USA.
¹⁴ Department of Medicine, Carbone Cancer Center, University of Wisconsin, Madison, WI, USA.
¹⁵ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶ Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁷ Department of Urologic Surgery, Vanderbilt Prostate Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁸ Department of Medicine, University of Washington and VAPSHCS GRECC, Seattle, WA, USA.
¹⁹ Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁰ Dame Roma Mitchell Cancer Research Laboratories and Freemasons Foundation Centre for Men's Health, Adelaide Medical School, The University of Adelaide, SA, Australia.
²¹ Prostate Cancer Foundation, Santa Monica, CA, USA.
²² Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
²³ Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA. Electronic address: dehm@umn.edu.
²⁴ Department of Urology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Urology and Pharmacology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA. Electronic address: ganesh.raj@utsouthwestern.edu.

PMID: 29258679
PMCID: PMC5929166
DOI: 10.1016/j.eururo.2017.11.038

Review

Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting

Jun Luo et al. Eur Urol. 2018 May.

. 2018 May;73(5):715-723.

doi: 10.1016/j.eururo.2017.11.038. Epub 2017 Dec 16.

Authors

Affiliations

¹ Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jluo1@jhmi.edu.
² The Institute of Cancer Research, London, UK.
³ Hematology-Oncology Division, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁴ Department of Surgery & Cancer, Imperial College London, Imperial Centre for Translational & Experimental Medicine (ICTEM), Hammersmith Hospital Campus, London, UK.
⁵ Department of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, FL, USA.
⁶ Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
⁷ Department of Urologic Sciences, University of British Columbia, The Vancouver Prostate Centre, Vancouver, BC, Canada.
⁸ Division of Clinical Studies, The Institute of Cancer Research, London, UK.
⁹ Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA.
¹⁰ Department of Urology, University of California Davis, Sacramento, CA, USA.
¹¹ Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Urology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; Department of Hematology/Medical Oncology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
¹² Department of Urology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
¹³ McDermott Center for Human Growth and Development, UT Southwestern Medical Center, Dallas, TX, USA.
¹⁴ Department of Medicine, Carbone Cancer Center, University of Wisconsin, Madison, WI, USA.
¹⁵ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
¹⁶ Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁷ Department of Urologic Surgery, Vanderbilt Prostate Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁸ Department of Medicine, University of Washington and VAPSHCS GRECC, Seattle, WA, USA.
¹⁹ Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁰ Dame Roma Mitchell Cancer Research Laboratories and Freemasons Foundation Centre for Men's Health, Adelaide Medical School, The University of Adelaide, SA, Australia.
²¹ Prostate Cancer Foundation, Santa Monica, CA, USA.
²² Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
²³ Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA; Department of Urology, University of Minnesota, Minneapolis, MN, USA. Electronic address: dehm@umn.edu.
²⁴ Department of Urology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA; Department of Urology and Pharmacology, UT Southwestern Medical Center at Dallas, Dallas, TX, USA. Electronic address: ganesh.raj@utsouthwestern.edu.

PMID: 29258679
PMCID: PMC5929166
DOI: 10.1016/j.eururo.2017.11.038

Abstract

Context: Although a number of studies have demonstrated the importance of constitutively active androgen receptor variants (AR-Vs) in prostate cancer, questions still remain about the precise role of AR-Vs in the progression of castration-resistant prostate cancer (CRPC).

Objective: Key stakeholders and opinion leaders in prostate cancer convened on May 11, 2017 in Boston to establish the current state of the field of AR-Vs.

Evidence acquisition: The meeting "Mission Androgen Receptor Variants" was the second of its kind sponsored by the Prostate Cancer Foundation (PCF). This invitation-only event was attended by international leaders in the field and representatives from sponsoring organizations (PCF and industry sponsors). Eighteen faculty members gave short presentations, which were followed by in-depth discussions. Discussions focused on three thematic topics: (1) potential of AR-Vs as biomarkers of therapeutic resistance; (2) role of AR-Vs as functionally active CRPC progression drivers; and (3) utility of AR-Vs as therapeutic targets in CRPC.

Evidence synthesis: The three meeting organizers synthesized this meeting report, which is intended to summarize major data discussed at the meeting and identify key questions as well as strategies for addressing these questions. There was a critical consensus that further study of the AR-Vs is an important research focus in CRPC. Contrasting views and emphasis, each supported by data, were presented at the meeting, discussed among the participants, and synthesized in this report.

Conclusions: This article highlights the state of knowledge and outlines the most pressing questions that need to be addressed to advance the AR-V field.

Patient summary: Although further investigation is needed to delineate the role of androgen receptor (AR) variants in metastatic castration-resistant prostate cancer, advances in measurement science have enabled development of blood-based tests for treatment selection. Detection of AR variants (eg, AR-V7) identified a patient population with poor outcomes to existing AR-targeting therapies, highlighting the need for novel therapeutic agents currently under development.

Keywords: Abiraterone; Androgen receptor variant 7; Androgen receptor variants; Castration-resistant prostate cancer; Enzalutamide.

PubMed Disclaimer

Conflict of interest statement

Financial disclosures: Other authors have no disclosure relevant to the subject matter.

Figures

**Fig. 1**
Transcript structure for representative AR-Vs. Stop codon positions are marked for each AR transcript. AR = androgen receptor; AR-FL = full length androgen receptor; AR-V = androgen receptor variant; E1–E8 = canonical androgen receptor exons 1–8; CE1–5 = cryptic exons 1–5; Ex = unknown exon in AR-V3.

See this image and copyright information in PMC

Comment in

Androgen Receptor Variants and Castration-resistant Prostate Cancer: Looking Back and Looking Forward.
Uo T, Sprenger C. Uo T, et al. Eur Urol. 2018 May;73(5):724-726. doi: 10.1016/j.eururo.2017.12.020. Epub 2018 Jan 3. Eur Urol. 2018. PMID: 29306511 No abstract available.

References

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1. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364:1995–2005. - PMC - PubMed
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1. Karantanos T, Evans CP, Tombal B, Thompson TC, Montironi R, Isaacs WB. Understanding the mechanisms of androgen deprivation resistance in prostate cancer at the molecular level. Eur Urol. 2015;67:470–9. - PMC - PubMed

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Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting

Affiliations

Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials