New and emerging HDAC inhibitors for cancer treatment

Area of Science:

• Oncology
• Epigenetics
• Molecular Biology

Background:

• Epigenetic enzymes, including histone deacetylases (HDACs), are frequently dysregulated in human tumors.
• This dysregulation occurs via mutation, altered expression, or aberrant protein recruitment.
• Targeting the cancer epigenome with small-molecule inhibitors is a rapidly developing field.

Purpose of the Study:

• To discuss the role of aberrant histone deacetylase (HDAC) regulation in tumorigenesis.
• To review histone deacetylase inhibitors (HDACis) targeting Class I, II, and IV HDACs.
• To examine the development of HDACis as anticancer agents.

Main Methods:

• Review of current literature on HDACs and HDAC inhibitors in cancer.
• Analysis of HDAC inhibitor development pipelines.
• Consideration of FDA-approved HDAC inhibitors (vorinostat, romidepsin) as benchmarks.

Main Results:

• Aberrantly regulated HDACs significantly influence cancer development.
• Numerous HDAC inhibitors targeting Class I, II, and IV HDACs are in development.
• The success of vorinostat and romidepsin supports the therapeutic potential of HDACis.

Conclusions:

• Histone deacetylase inhibitors represent a promising class of anticancer therapeutics.
• Targeting specific HDAC classes offers a refined approach to epigenetic cancer therapy.
• Continued development of HDACis is warranted for improved cancer treatment strategies.