The clinical development of histone deacetylase inhibitors as targeted anticancer drugs

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Histone deacetylase (HDAC) inhibitors represent a novel class of targeted anticancer therapeutics.
• The precise biological roles of the 11 human zinc-dependent HDACs remain incompletely elucidated.
• HDACs are lysine deacetylases involved in various cellular processes, with non-redundant functions.

Purpose of the Study:

• To review the mechanisms of action of HDAC inhibitors.
• To explore how HDAC inhibitors selectively induce cancer cell death, growth arrest, and inhibit angiogenesis.
• To discuss the current clinical and preclinical development of various HDAC inhibitor classes.

Main Methods:

• Review of preclinical and clinical studies on HDAC inhibitors.
• Focus on the molecular mechanisms underlying HDAC inhibitor-induced cancer cell death.
• Analysis of the anti-cancer activities including growth arrest, mobility inhibition, and antiangiogenesis.

Main Results:

• HDAC inhibitors induce transformed cell growth arrest and apoptosis.
• HDAC inhibitors exhibit anti-mobility and antiangiogenesis effects.
• Numerous HDAC inhibitors (hydroxamates, cyclic peptides, etc.) are in clinical trials, with potential for targeting specific HDACs.

Conclusions:

• Preclinical and limited clinical data suggest HDAC inhibitors are most effective in combination therapies.
• Combination with cytotoxic or other targeted anticancer agents is recommended for enhanced therapeutic benefit.
• HDAC inhibitors hold significant potential as part of multifaceted cancer treatment strategies.