Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
The Institute of Cancer Research, London, UK.
Eur Urol. 2018 May;73(5):715-723. doi: 10.1016/j.eururo.2017.11.038. Epub 2017 Dec 16.
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).
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.
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.
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.
This article highlights the state of knowledge and outlines the most pressing questions that need to be addressed to advance the AR-V field.
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.
虽然许多研究已经证明了雄激素受体变异体（AR-V）在前列腺癌中的重要性，但关于 AR-V 在去势抵抗性前列腺癌（CRPC）进展中的确切作用仍存在疑问。
前列腺癌的主要利益相关者和意见领袖于 2017 年 5 月 11 日在波士顿聚会，旨在确定 AR-V 领域的现状。
此次会议名为“雄激素受体变异体使命”，是由前列腺癌基金会（PCF）主办的第二次会议。该会议邀请了该领域的国际领导者以及赞助组织（PCF 和行业赞助商）的代表参加。18 位教员进行了简短的演讲，随后进行了深入的讨论。讨论集中在三个主题上：（1）AR-V 作为治疗抵抗生物标志物的潜力；（2）AR-V 作为功能性活跃的 CRPC 进展驱动因素的作用；（3）AR-V 在 CRPC 中的治疗靶点的实用性。
三位会议组织者综合了这份会议报告，旨在总结会议上讨论的主要数据，并确定关键问题以及解决这些问题的策略。会议形成了一个重要共识，即进一步研究 AR-V 是 CRPC 中的一个重要研究重点。会议上提出了相互矛盾的观点和重点，每个观点都有数据支持，与会者进行了讨论，并在本报告中进行了综合。
本文突出了知识的现状，并概述了推进 AR-V 领域最紧迫的问题。
虽然需要进一步研究来阐明雄激素受体（AR）变异体在转移性去势抵抗性前列腺癌中的作用，但测量科学的进步已经使得开发基于血液的治疗选择测试成为可能。检测 AR 变体（例如，AR-V7）确定了对现有 AR 靶向治疗反应不佳的患者人群，这突显了对目前正在开发的新型治疗药物的需求。
