Targeting histone methylation for cancer therapy: enzymes, inhibitors, biological activity and perspectives

Area of Science:

• Epigenetics and Molecular Biology
• Cancer Therapeutics

Background:

• Post-translational methylation of histones regulates gene expression.
• Aberrant histone methylation is linked to cancer development.
• Histone methylation modulators are emerging as potential therapeutic agents.

Purpose of the Study:

• To review cancer-relevant histone methylation enzymes.
• To summarize small molecule inhibitors targeting these enzymes.
• To discuss preclinical and clinical antitumor activities and future perspectives.

Main Methods:

• Literature review of biochemistry, structures, and biology of histone methylation enzymes.
• Analysis of small molecule inhibitors' development and activity.
• Summary of preclinical and clinical data for cancer therapy.

Main Results:

• Numerous potent and selective histone methylation inhibitors have been developed.
• Extensive preclinical studies demonstrate biological activity.
• Several compounds are in clinical trials for safety, pharmacokinetics, and efficacy in cancer patients.

Conclusions:

• Small molecule inhibitors offer a novel therapeutic strategy for cancer.
• Targeting histone methylation is a rapidly expanding field with significant clinical potential.
• Further research and clinical development are ongoing for these epigenetic therapies.