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Review
. 2016 May;33(5):44.
doi: 10.1007/s12032-016-0759-3. Epub 2016 Apr 4.

Targeting persistent androgen receptor signaling in castration-resistant prostate cancer

Laura Graham  1 , Michael T Schweizer  2
Affiliations
Review

Targeting persistent androgen receptor signaling in castration-resistant prostate cancer

Laura Graham et al. Med Oncol. 2016 May.

Abstract

Castration-resistant prostate cancer (CRPC), the invariably lethal phenotype of advanced prostate cancer, represents a clinical state defined by disease progression despite reduction of testosterone to castrate levels (i.e., ≤50 ng/dL). Although resistant to androgen-deprivation therapy (i.e., LHRH agonists/antagonists), CRPC continues to depend on the androgen receptor (AR)-signaling pathway. Supporting the importance of AR-signaling in a castration-resistant state, the next-generation AR-signaling inhibitors enzalutamide and abiraterone have been shown to afford a survival benefit in men with metastatic CRPC. However, primary and secondary resistance mechanisms to these agents inevitably drive continued disease progression-often as a result of re-activation of AR-signaling. With increased understanding of the mechanisms underlying how continued AR-signaling occurs in spite of drugs like abiraterone and enzalutamide, a new wave of therapies is emerging designed to more effectively target AR-signaling. This review will focus on the more clinically relevant mechanisms of CRPC drug resistance and our ongoing efforts to develop drugs to target these mechanisms.

Keywords: Abiraterone; Androgen receptor; Androgen receptor splice variant; Androgen-deprivation therapy; Castration-resistant prostate cancer; Drug resistance; Enzalutamide; Hormonal therapy.

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References

    1. Ann Oncol. 2012 Sep;23(9):2399-2408 - PubMed
    1. J Clin Oncol. 2015 May 10;33(14):1601-8 - PubMed
    1. Cell. 2015 May 21;161(5):1215-1228 - PubMed
    1. Clin Cancer Res. 2011 Sep 15;17(18):5913-25 - PubMed
    1. N Engl J Med. 2013 Jan 10;368(2):138-48 - PubMed

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