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Molecular determinants of response to high-dose androgen therapy in prostate cancer.

ABSTRACT: Clinical trials of high-dose androgen (HDA) therapy for prostate cancer (PC) have shown promising efficacy but are limited by lack of criteria to identify likely responders. To elucidate factors that govern the growth-repressive effects of HDAs, we applied an unbiased integrative approach using genetic screens and transcriptional profiling of PC cells with or without demonstrated phenotypic sensitivity to androgen-mediated growth repression. Through this comprehensive analysis, we identified genetic events and related signaling networks that determine the response to both HDA and androgen withdrawal. We applied these findings to develop a gene signature that may serve as an early indicator of treatment response and identify men with tumors that are amenable to HDA therapy.

SUBMITTER: Nyquist MD

PROVIDER: S-EPMC6795499 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Molecular determinants of response to high-dose androgen therapy in prostate cancer.

Nyquist Michael D MD Corella Alexandra A Mohamad Osama O Coleman Ilsa I Kaipainen Arja A Kuppers Daniel A DA Lucas Jared M JM Paddison Patrick J PJ Plymate Stephen R SR Nelson Peter S PS Mostaghel Elahe A EA

JCI insight 20191003 19

Clinical trials of high-dose androgen (HDA) therapy for prostate cancer (PC) have shown promising efficacy but are limited by lack of criteria to identify likely responders. To elucidate factors that govern the growth-repressive effects of HDAs, we applied an unbiased integrative approach using genetic screens and transcriptional profiling of PC cells with or without demonstrated phenotypic sensitivity to androgen-mediated growth repression. Through this comprehensive analysis, we identified gen ...[more]

PMID: 31503550

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Molecular determinants of response to high dose androgen therapy in prostate cancer

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