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Targeting anti-androgen therapy resistance through epigenetic rewiring

Although resistance develops in response to androgen receptor-targeted therapy in advanced prostate cancer, the underlying mechanisms remain unclear. The protein ZMYND8 is now shown to bind FOXM1 and the SWI–SNF complex, promoting the onset of neuroendocrine prostate cancer, which can thus be abrogated through small-molecule ZMYND8 inhibition.

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Fig. 1: The AR inhibitor ENZ induces ZMYND8-dependent epigenetic alterations involving FOXM1 and the SWI–SNF complex, which drives the CRPC-to-NEPC transition and can be targeted by a small molecule.

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Authors and Affiliations

Weill Cornell Graduate School of Medical Sciences, New York, NY, USA

Kate E. Dunmore

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA

Kate E. Dunmore & David S. Rickman

Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA

David S. Rickman

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Kate E. Dunmore

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2. David S. Rickman

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Correspondence to David S. Rickman.

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Dunmore, K.E., Rickman, D.S. Targeting anti-androgen therapy resistance through epigenetic rewiring. Nat Cancer (2025). https://doi.org/10.1038/s43018-025-00906-5

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Published:18 March 2025

DOI:https://doi.org/10.1038/s43018-025-00906-5

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