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Updated: May 9, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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The mechanism of histone modifications in regulating enzalutamide sensitivity in advanced prostate cancer

Zhite Zhao1, Yuming Jing1, Zhicheng Xu1

  • 1Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.

International Journal of Biological Sciences
|April 30, 2025
PubMed

Insights

Histone modifications in prostate cancer (PCa) drive resistance to enzalutamide (Enz) treatment. Understanding these changes offers new combination therapy strategies to improve CRPC outcomes.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Prostate cancer (PCa) is a leading global cancer in men.
  • Castration-resistant prostate cancer (CRPC) poses significant treatment challenges, especially resistance to enzalutamide (Enz).
  • Histone modifications, including methylation and acetylation, are implicated in the development of Enz resistance.

Purpose of the Study:

  • To review recent findings on how histone modification patterns change during PCa progression and drug resistance.
  • To explore the role of the tumor microenvironment's signaling pathways in regulating histone-modifying enzymes.
  • To discuss potential combination therapies for overcoming Enz resistance in PCa.

Main Methods:

  • Literature review of studies investigating histone modifications in PCa and Enz resistance.
  • Analysis of research on signaling pathways affecting histone-modifying enzymes.
  • Synthesis of current knowledge on therapeutic strategies targeting epigenetic alterations.

Main Results:

  • Altered histone methylation and acetylation patterns are linked to Enz resistance in CRPC.
  • Changes in histone modifications occur in drug resistance-related genes as PCa progresses.
  • Tumor microenvironment signaling pathways influence histone-modifying enzyme activity, impacting Enz efficacy.

Conclusions:

  • Histone modification patterns are critical determinants of enzalutamide efficacy in prostate cancer.
  • Targeting epigenetic alterations offers promising avenues for novel therapeutic strategies.
  • Combination therapies hold potential for reversing drug resistance and improving clinical outcomes in CRPC.
Keywords:
drug resistanceenzalutamidehistone modificationsprostate cancer

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