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Comment
. 2013 Sep;3(9):971-4.
doi: 10.1158/2159-8290.CD-13-0405.

Resistance emerges to second-generation antiandrogens in prostate cancer

William G Nelson  1 , Srinivasan Yegnasubramanian
Affiliations
Comment

Resistance emerges to second-generation antiandrogens in prostate cancer

William G Nelson et al. Cancer Discov. 2013 Sep.

Abstract

The appearance of a mutant androgen receptor, AR(F876L), in prostate cancer cells chronically exposed to enzalutamide or ARN-509 promotes a switch from antagonist to agonist receptor function, undermining the potential long-term effectiveness of these second-generation antiandrogen drugs.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Figures

Figure 1
Figure 1. Mechanisms of Resistance to AR-Directed Therapies
Despite treatment with androgen deprivation therapy (ADT) or first generation anti-androgens, prostate cancers progress to castration-resistance, often with emergence of an AR-dependent resistant phenotype that is sensitive to treatment with second generation anti-androgens such as enzalutamide or ARN-509. However, AR-dependent resistance emerges again, this time driven by mutant AR. This tendency to maintain AR addiction will permit treatment with next generation AR antagonists. If prostate cancer clones appear at any time during disease progression that have escaped AR addiction, such treatments will prove ineffective.
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Comment on

References

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