Histone deacetylase inhibitors and colorectal cancer: what is new?

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Colorectal cancer is a leading global cancer, often driven by genetic defects affecting tumor suppressor genes and oncogenes.
• Chromatin modifications, regulated by histone acetyltransferases and histone deacetylases, play a crucial role in cancer gene expression.
• Histone deacetylase inhibitors (HDACis) are emerging as potential therapeutic agents due to their antiproliferative effects and favorable toxicity profile in solid tumors.

Purpose of the Study:

• To explore the potential of histone deacetylase inhibitors (HDACis) as a therapeutic strategy for colorectal cancer.
• To review the current experimental and clinical evidence for HDACis in colorectal cancer treatment, including monotherapy and combination approaches.

Main Methods:

• Review of existing literature on histone deacetylase inhibitors in colorectal cancer.
• Analysis of preclinical and clinical trial data regarding the efficacy and safety of HDACis.
• Examination of combination therapies involving HDACis with conventional chemotherapy or other agents like decitabine.

Main Results:

• Histone deacetylase inhibitors demonstrate antiproliferative activities and a relatively low toxicity profile in solid tumors, including colorectal cancer.
• Vorinostat, a histone deacetylase inhibitor, has shown ability to stabilize advanced colorectal cancer in clinical trials when used with conventional chemotherapy.
• Experimental data suggests that combining vorinostat with decitabine (a DNA methyl transferase inhibitor) may yield optimal outcomes.

Conclusions:

• Histone deacetylase inhibitors represent a promising therapeutic avenue for colorectal cancer, with current evidence primarily from experimental studies.
• Combination therapies involving histone deacetylase inhibitors, with chemotherapy or other targeted agents, warrant further investigation.
• Randomized clinical trials are essential to definitively evaluate the efficiency and establish the role of histone deacetylase inhibitors in colorectal cancer management.