2. Academic Validation
  3. Roles of KDM5 demethylases in therapeutic resistance of cancers

Roles of KDM5 demethylases in therapeutic resistance of cancers

  • Epigenetics Chromatin. 2025 Sep 26;18(1):61. doi: 10.1186/s13072-025-00624-3.
Xiaobo Chen # 1 2,  Manjun Chen # 2,  Xingkun Gu # 2,  Qinghua Zhou 1,  Yunping Zhao 2,  Yanlong Yang 2,  Hongwei Zhang 2,  Xudong Yang 3 4
Affiliations

Affiliations

  • 1 Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Sichuan, 610065, Chengdu, P. R. China.
  • 2 Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Wuhua District, Kunming, 650032, Yunnan, P.R. China.
  • 3 Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Sichuan, 610065, Chengdu, P. R. China. [email protected].
  • 4 Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Wuhua District, Kunming, 650032, Yunnan, P.R. China. [email protected].
  • # Contributed equally.
PMID: 41013520 DOI: 10.1186/s13072-025-00624-3
Abstract

Epigenetic modifications, including the regulation of histone H3 lysine 4 methylation (H3K4me2/3), play critical roles in maintaining normal tissue homeostasis and influencing the progression of Cancer, including growth, invasion, metastasis, and therapeutic resistance. The demethylation of H3K4me2/3 is orchestrated by the KDM5 demethylase family, comprising KDM5A, KDM5B, KDM5C, and KDM5D. Recent studies have highlighted the pivotal role of KDM5 demethylases in mediating resistance to Cancer therapies, encompassing chemoresistance, radioresistance, immune evasion, and targeted therapy resistance. This review provides a comprehensive overview of the regulatory mechanisms by which KDM5 demethylases contribute to these resistance pathways, with a focus on their molecular targets and interactions within the tumor microenvironment. Furthermore, we discuss emerging therapeutic strategies aimed at overcoming treatment resistance by targeting KDM5 demethylases. These insights provide a foundation for the development of innovative therapeutic interventions to enhance the efficacy of existing Cancer treatments, offering a transformative approach to improving long-term patient survival and quality of life.

Keywords

Cancer; Histone methylation; Immune evasion; KDM5 demethylases; Therapeutic resistance.

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