Targeting histone deacetylases for cancer therapy: Trends and challenges

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Dysregulation of histone deacetylases (HDACs) is linked to cancer development and progression.
• Five HDAC inhibitors (HDACis) are approved, but traditional agents cause toxicities and are less effective against solid tumors.
• Development of next-generation HDACis is crucial for improved cancer therapy.

Purpose of the Study:

• To review the biological functions and oncogenic roles of HDACs.
• To explore structural features of HDAC isoforms and the development of isoform-selective inhibitors.
• To discuss combination therapies, multitarget agents, and HDAC PROTACs for novel anticancer strategies.

Main Methods:

• Literature review of HDAC functions, roles in oncogenesis, and inhibitor development.
• Analysis of structural features of different HDAC isoforms.
• Investigation of emerging therapeutic strategies including combination therapies, multitarget agents, and HDAC PROTACs.

Main Results:

• HDACs play critical roles in tumor development and progression.
• Current HDACis have limitations including off-target toxicities and low sensitivity in solid tumors.
• Next-generation strategies like isoform-selective inhibitors, combination therapies, and HDAC PROTACs offer potential for enhanced anticancer effects with reduced adverse events.

Conclusions:

• Novel HDAC inhibitors with improved isoform selectivity, efficacy, and safety profiles are needed.
• Targeting HDACs through innovative approaches like multitarget agents and PROTACs holds promise for overcoming limitations of current therapies.
• Further research into next-generation HDACis can inspire the development of more effective and safer anticancer treatments.