Related Experiment Video

Updated: Jan 4, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

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Androgen Receptor Interaction with Mediator Complex Is Enhanced in Castration-Resistant Prostate Cancer by CDK7

Joshua W Russo1, Mannan Nouri1, Steven P Balk2

  • 1Hematology-Oncology Division, Department of Medicine and Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Cancer Discovery
|November 3, 2019
PubMed

Insights

Researchers found that CDK7 phosphorylation of MED1 enhances androgen receptor (AR) interaction, a process upregulated in advanced prostate cancer. Inhibiting CDK7 with THZ1 suppressed enzalutamide resistance and reduced tumors, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Prostate cancer often develops resistance to castration and enzalutamide therapies.
  • The androgen receptor (AR) signaling pathway is crucial in prostate cancer progression.
  • Understanding resistance mechanisms is vital for developing effective treatments.

Purpose of the Study:

  • To investigate the role of CDK7 in mediating androgen receptor (AR) function in prostate cancer.
  • To explore the therapeutic potential of CDK7 inhibition in overcoming enzalutamide resistance.

Main Methods:

  • Analysis of MED1 phosphorylation by CDK7 in prostate cancer cells.
  • Assessment of AR-MED1 interaction and chromatin recruitment.
  • Evaluation of the efficacy of the CDK7 inhibitor THZ1 in vitro and in vivo models.

Main Results:

  • CDK7 phosphorylates MED1, enhancing its interaction with AR.
  • This phosphorylation is elevated in castration-resistant and enzalutamide-resistant prostate cancer.
  • THZ1 treatment inhibited AR-mediated MED1 recruitment and suppressed enzalutamide resistance.
  • THZ1 induced tumor regression in a castration-resistant prostate cancer xenograft model.

Conclusions:

  • CDK7-mediated phosphorylation of MED1 is a key mechanism in advanced prostate cancer.
  • Targeting CDK7 with THZ1 represents a promising therapeutic strategy for resistant prostate cancer.
  • This study identifies a novel vulnerability in advanced prostate cancer treatment.

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