Trend of histone deacetylase inhibitors in cancer therapy: isoform selectivity or multitargeted strategy

Area of Science:

• Biochemistry and Molecular Biology
• Pharmacology and Drug Discovery
• Oncology

Background:

• Pharmacological inhibition of histone deacetylases (HDACs) is a validated therapeutic strategy across multiple disease areas.
• Histone deacetylase inhibitors (HDACIs) demonstrate significant efficacy as antitumor agents in preclinical and clinical investigations.
• HDACs play crucial roles in gene regulation, making them attractive targets for therapeutic intervention.

Purpose of the Study:

• To review and compare two distinct strategies for designing HDAC inhibitors (HDACIs) in cancer therapy.
• To provide insights into the development of selective versus dual/multitargeted HDACIs.
• To analyze the achievements and potential of different HDACI design approaches for anticancer applications.

Main Methods:

• Literature review of existing strategies for HDACI design.
• Analysis of research focusing on highly selective HDACIs.
• Evaluation of studies investigating dual- or multitargeted HDACIs.

Main Results:

• Both highly selective and multitargeted HDACI design strategies have yielded effective antitumor agents.
• Selective inhibitors aim to elucidate individual HDAC functions and minimize side effects.
• Multitargeted inhibitors, though less explored, show promising potential for enhanced antitumor efficacy.

Conclusions:

• Effective HDACIs have been developed through both selective and multitargeted design approaches.
• The choice of strategy depends on the specific therapeutic goals and understanding of HDAC functions.
• Continued research into both strategies is crucial for advancing HDACI-based cancer therapy.