Role of Androgen Receptor Variants in Prostate Cancer

Report from the 2017 Mission Androgen Receptor Variants Meeting

Jun Luo, Gerhardt Attard, Steven P. Balk, Charlotte Bevan, Kerry Burnstein, Laura Cato, Artem Cherkasov, Johann S. De Bono, Yan Dong, Allen C. Gao, Martin Gleave, Hannelore Heemers, Mayuko Kanayama, Ralf Kittler, Joshua M. Lang, Richard J. Lee, Christopher J. Logothetis, Robert Matusik, Stephen Plymate, Charles L. Sawyers & 7 others Luke A. Selth, Howard Soule, Wayne Tilley, Nancy L. Weigel, Amina Zoubeidi, Scott M. Dehm, Ganesh V. Raj

Research output: Contribution to journalArticle

22 Citations (Scopus)

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. Precision detection methods for androgen receptor variants have been developed and will enable treatment selection in men with castration-resistant prostate cancer. Further investigation is needed, and there is a pressing need to develop novel therapeutic approaches to overcome this putative resistance mechanism.

Original languageEnglish (US)
Pages (from-to)715-723
Number of pages9
JournalEuropean Urology
Volume73
Issue number5
DOIs
StatePublished - May 1 2018

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Androgen Receptors
Prostatic Neoplasms
Castration
Therapeutics
Hematologic Tests
Industry

Keywords

  • Abiraterone
  • Androgen receptor variant 7
  • Androgen receptor variants
  • Castration-resistant prostate cancer
  • Enzalutamide

ASJC Scopus subject areas

  • Urology

Cite this

Role of Androgen Receptor Variants in Prostate Cancer : Report from the 2017 Mission Androgen Receptor Variants Meeting. / Luo, Jun; Attard, Gerhardt; Balk, Steven P.; Bevan, Charlotte; Burnstein, Kerry; Cato, Laura; Cherkasov, Artem; De Bono, Johann S.; Dong, Yan; Gao, Allen C.; Gleave, Martin; Heemers, Hannelore; Kanayama, Mayuko; Kittler, Ralf; Lang, Joshua M.; Lee, Richard J.; Logothetis, Christopher J.; Matusik, Robert; Plymate, Stephen; Sawyers, Charles L.; Selth, Luke A.; Soule, Howard; Tilley, Wayne; Weigel, Nancy L.; Zoubeidi, Amina; Dehm, Scott M.; Raj, Ganesh V.

In: European Urology, Vol. 73, No. 5, 01.05.2018, p. 715-723.

Research output: Contribution to journalArticle

Luo, J, Attard, G, Balk, SP, Bevan, C, Burnstein, K, Cato, L, Cherkasov, A, De Bono, JS, Dong, Y, Gao, AC, Gleave, M, Heemers, H, Kanayama, M, Kittler, R, Lang, JM, Lee, RJ, Logothetis, CJ, Matusik, R, Plymate, S, Sawyers, CL, Selth, LA, Soule, H, Tilley, W, Weigel, NL, Zoubeidi, A, Dehm, SM & Raj, GV 2018, 'Role of Androgen Receptor Variants in Prostate Cancer: Report from the 2017 Mission Androgen Receptor Variants Meeting', European Urology, vol. 73, no. 5, pp. 715-723. https://doi.org/10.1016/j.eururo.2017.11.038
Luo, Jun ; Attard, Gerhardt ; Balk, Steven P. ; Bevan, Charlotte ; Burnstein, Kerry ; Cato, Laura ; Cherkasov, Artem ; De Bono, Johann S. ; Dong, Yan ; Gao, Allen C. ; Gleave, Martin ; Heemers, Hannelore ; Kanayama, Mayuko ; Kittler, Ralf ; Lang, Joshua M. ; Lee, Richard J. ; Logothetis, Christopher J. ; Matusik, Robert ; Plymate, Stephen ; Sawyers, Charles L. ; Selth, Luke A. ; Soule, Howard ; Tilley, Wayne ; Weigel, Nancy L. ; Zoubeidi, Amina ; Dehm, Scott M. ; Raj, Ganesh V. / Role of Androgen Receptor Variants in Prostate Cancer : Report from the 2017 Mission Androgen Receptor Variants Meeting. In: European Urology. 2018 ; Vol. 73, No. 5. pp. 715-723.
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T2 - Report from the 2017 Mission Androgen Receptor Variants Meeting

AU - Luo, Jun

AU - Attard, Gerhardt

AU - Balk, Steven P.

AU - Bevan, Charlotte

AU - Burnstein, Kerry

AU - Cato, Laura

AU - Cherkasov, Artem

AU - De Bono, Johann S.

AU - Dong, Yan

AU - Gao, Allen C.

AU - Gleave, Martin

AU - Heemers, Hannelore

AU - Kanayama, Mayuko

AU - Kittler, Ralf

AU - Lang, Joshua M.

AU - Lee, Richard J.

AU - Logothetis, Christopher J.

AU - Matusik, Robert

AU - Plymate, Stephen

AU - Sawyers, Charles L.

AU - Selth, Luke A.

AU - Soule, Howard

AU - Tilley, Wayne

AU - Weigel, Nancy L.

AU - Zoubeidi, Amina

AU - Dehm, Scott M.

AU - Raj, Ganesh V.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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. Precision detection methods for androgen receptor variants have been developed and will enable treatment selection in men with castration-resistant prostate cancer. Further investigation is needed, and there is a pressing need to develop novel therapeutic approaches to overcome this putative resistance mechanism.

AB - 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. Precision detection methods for androgen receptor variants have been developed and will enable treatment selection in men with castration-resistant prostate cancer. Further investigation is needed, and there is a pressing need to develop novel therapeutic approaches to overcome this putative resistance mechanism.

KW - Abiraterone

KW - Androgen receptor variant 7

KW - Androgen receptor variants

KW - Castration-resistant prostate cancer

KW - Enzalutamide

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