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Updated: Dec 16, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Targeting the KDM4B-AR-c-Myc axis promotes sensitivity to androgen receptor-targeted therapy in advanced prostate

Dong-E Tang1, Yong Dai1, Jia-Xi He2

  • 1Department of Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital Southern University of Science and Technology, Shenzhen People's Hospital, Shenzhen, PR China.

The Journal of Pathology
|July 4, 2020
PubMed

Insights

Histone demethylase KDM4B promotes resistance to prostate cancer therapies by increasing c-Myc expression. Inhibiting KDM4B may overcome this resistance, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • The histone demethylase KDM4B is a co-activator for the androgen receptor (AR), influencing gene expression via H3K9 methylation.
  • Constitutively active AR drives anti-androgen resistance in advanced prostate cancer, but KDM4B's role in resistance to newer therapies is unclear.

Purpose of the Study:

  • To investigate the role of KDM4B in enzalutamide-resistant prostate cancer.
  • To elucidate the mechanisms by which KDM4B contributes to anti-androgen resistance.

Main Methods:

  • Analysis of KDM4B expression in enzalutamide-resistant prostate cancer cells and patient samples.
  • Investigating the effect of KDM4B overexpression/inhibition on AR recruitment, H3K9 demethylation, and c-Myc transcription.
  • Evaluating the therapeutic potential of KDM4B inhibition in preclinical xenograft models.

Main Results:

  • KDM4B is overexpressed in enzalutamide-resistant prostate cancer cells.
  • KDM4B overexpression enhances AR binding to the c-Myc enhancer, leading to increased c-Myc transcription and promoting resistance.
  • KDM4B inhibition suppressed tumor growth, improved enzalutamide efficacy by reducing c-Myc, and correlated with poor prognosis in patients.

Conclusions:

  • KDM4B drives anti-androgen resistance in prostate cancer through epigenetic regulation of c-Myc.
  • Targeting KDM4B offers a potential strategy to overcome resistance to AR-targeted therapies by reducing AR-dependent c-Myc expression.
Keywords:
KDM4Bandrogen receptorc-Myccastration-resistant prostate cancerenzalutamide resistancehistone demethylaseprostate cancer

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