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Roles of KDM5 demethylases in therapeutic resistance of cancers

Xiaobo Chen1,2, Manjun Chen2, Xingkun Gu2

  • 1Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Sichuan, 610065, Chengdu, P. R. China.

Epigenetics & Chromatin
|September 27, 2025
PubMed

Insights

Histone modifications like H3K4me2/3 are key in cancer. KDM5 demethylases drive resistance to cancer therapies, but targeting them offers new treatment strategies.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Histone H3 lysine 4 methylation (H3K4me2/3) is crucial for tissue homeostasis and cancer progression.
  • The KDM5 demethylase family (KDM5A-D) regulates H3K4me2/3 demethylation.
  • KDM5 demethylases are increasingly recognized for their role in cancer therapy resistance.

Purpose of the Study:

  • To review the mechanisms by which KDM5 demethylases contribute to cancer therapy resistance.
  • To explore the molecular targets and tumor microenvironment interactions of KDM5 demethylases.
  • To discuss novel therapeutic strategies targeting KDM5 demethylases to overcome resistance.

Main Methods:

  • Literature review of epigenetic regulation in cancer.
  • Analysis of KDM5 demethylase family functions in cancer progression and resistance.
  • Synthesis of current research on therapeutic targeting of KDM5 demethylases.

Main Results:

  • KDM5 demethylases mediate resistance to chemotherapy, radiotherapy, immunotherapy, and targeted therapies.
  • These enzymes impact cancer growth, invasion, metastasis, and immune evasion.
  • Specific molecular targets and interactions within the tumor microenvironment are implicated.

Conclusions:

  • KDM5 demethylases are critical regulators of diverse cancer therapy resistance mechanisms.
  • Targeting KDM5 demethylases presents a promising strategy to enhance existing cancer treatments.
  • Further research into KDM5 demethylase pathways can lead to improved patient survival and quality of life.
Keywords:
CancerHistone methylationImmune evasionKDM5 demethylasesTherapeutic resistance

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