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. SawyersLuke A. Selth, Howard Soule, Wayne Tilley, Nancy L. Weigel, Amina Zoubeidi, Scott M. Dehm, Ganesh V. Raj

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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 2018

Bibliographical note

Funding Information:
The three meeting organizers (J.L., S.M.D., G.V.R.) conceived the idea of an invitation-only meeting focusing on AR-Vs. Three thematic topics were predefined prior to the meeting: (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. The meeting was sponsored by the PCF, Sanofi, Astellas, Janssen Research and Development LLC, and Sun Pharma, and held in Boston, MA, prior to the American Urological Association annual meeting. Academic physicians and scientists from the USA, the UK, Canada, Australia, and Japan, as well as representatives from four sponsoring pharmaceutical companies attended this meeting. Eighteen faculty members gave short presentations, which were followed by in-depth discussions. The three meeting organizers summarized major data discussed at the meeting, identified 26 key questions in the field, and synthesized this meeting report. The 26 key questions were included in an online survey sent to all nonindustry participants after the meeting. Detailed voting results (percent and number of approval votes) are included in the three boxes of the Supplementary material, summarizing general consensus reached at the meeting.

Funding Information:
Financial disclosures: Jun Luo certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Jun Luo has served as a paid consultant/advisor for Sun Pharma, Janssen, and Sanofi; has received research funding to his institution from Orion, Astellas, Sanofi, and Gilead; and is a coinventor of a technology that has been licensed to A&G, Tokai, and Qiagen. Gerhardt Attard received honoraria, speaker fees, and/or research support from and/or has conducted clinical trials for Astellas, Pfizer, Janssen, Sanofi, ESSA, and Arno that have an interest in targeting the androgen receptor in prostate cancer; and is included in the Institute of Cancer Research rewards to inventors list for abiraterone. Laura Cato is an employee at Sanofi-Genzyme. Johann S. De Bono served on advisory boards for multiple pharmaceutical and biotech partners including AstraZeneca, Astellas, Daiichi Sankyo, Genentech, Genmab, GSK, Merck Serono, MSD, Pfizer Oncology, Sanofi-Aventis, and Taiho; and is an employee of the Institute of Cancer Research, a not-for-profit research organization, which has a commercial interest in abiraterone acetate and PARP inhibitors for DNA repair defective cancers. Allen C. Gao has stock and other ownership interests in Pandomedx, Inc. Joshua M. Lang has Salus Discovery and LLC-ownership interest; and is a Sanofi consultant. Richard J. Lee is on the advisory board of Janssen. Christopher J. Logothetis is a coinventor of enzalutamide and entitled to royalties from the University of California. Scott M. Dehm has served as a paid consultant/advisor for Medivation/Astellas and Janssen Research and Development, LLC; and has received research funding from Janssen Research and Development, LLC. Ganesh V. Raj is the founder of C-diagnostics, GaudiumRx and EtiraRx, has received grants from Bayer and Janssen, and serves as a consultant/speaker for Janssen, Medivation/Pfizer, Astellas, Bayer, and Sanofi. Other authors have no disclosure relevant to the subject matter.

Publisher Copyright:
© 2017 European Association of Urology

Keywords

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

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