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Updated: Aug 30, 2025

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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Why ARNT Prostate Tumors Responding to Enzalutamide?

Meng Zhang1,2, Thaidy Moreno-Rodriguez1,3, David A Quigley1,3,4

  • 1Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California.

Cancer Discovery
|September 2, 2022
PubMed
Abstract

Insights

Prostate tumors can become resistant to therapies like enzalutamide. This resistance involves changes in transcription factors and the circadian protein ARNTL, revealing a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Circadian Biology

Background:

  • Prostate cancer often develops resistance to androgen receptor (AR)-targeted therapies.
  • Treatment-induced alterations in transcription factor activity can drive neuroendocrine differentiation.
  • Enzalutamide is a second-generation AR-targeted therapy used in prostate cancer treatment.

Discussion:

  • This study investigates the molecular mechanisms underlying treatment resistance in prostate cancer.
  • It explores the role of transcription factors in promoting neuroendocrine features.
  • The research highlights the involvement of circadian clock components in therapy resistance.

Key Insights:

  • The circadian protein ARNTL (also known as BMAL1) plays an unexpected role in resistance to enzalutamide.
  • ARNTL influences transcriptional changes associated with neuroendocrine prostate cancer.
  • This finding offers a novel perspective on overcoming therapeutic resistance.

Outlook:

  • Targeting ARNTL may represent a new strategy to overcome enzalutamide resistance.
  • Further research into circadian proteins could uncover additional therapeutic targets.
  • Understanding these mechanisms may lead to improved treatment outcomes for advanced prostate cancer.

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