Author(s)

Kefan Hu

Corresponding Author

Kefan Hu

Abstract

The KDM5 family is an epigenetic regulator with histone demethylase activity, consisting of four members, KDM5A-D. Through the JmjC domain, it removes H3K4me2/me3 modifications to regulate gene expression. It is abnormally expressed in breast cancer (especially KDM5A/B in TNBC and HER2-positive subtypes), and by silencing tumor suppressor genes and activating oncogenes, it regulates the cell cycle, promotes EMT, and disrupts the tumor microenvironment, thereby driving breast cancer proliferation, invasion, and drug resistance. Preclinical studies have shown that KDM5 inhibitors can suppress breast cancer cell growth, enhance the efficacy when combined with chemotherapy and targeted drugs, and that subtype-targeted therapies based on KDM5 expression and biomarker-guided personalized strategies have translational potential. However, current challenges include insufficient inhibitor specificity and difficulties in target selection due to breast cancer heterogeneity. In the future, it is necessary to develop highly specific inhibitors and optimize combination strategies to promote their integration into precision therapy systems for breast cancer.

Keywords

KDM5 Family; Breast Cancer; Epigenetic Regulation; Targeted Therapy