Histone Deacetylase Inhibitors and Colorectal Cancer: what is new?
Ekaterini C. Tampaki,
Christian A. Nebiker,
Colorectal cancer is the third most common cancer in humans. Cancer has always been regarded as a disease of genetic defects
such as gene mutations and deletions, chromosomal abnormalities, which lead to the loss of function of tumor-suppressor genes and/or
gain of function or hyperactivation of oncogenes. Modifications on chromatin are considered to be the result of the opposing activities of
histone acetyltransferases and histone deacetylases, which affect gene expression. Targeting histone deacetylases, histone deacetylase
inhibitors are promising agents, as in solid tumors they are characterized by relatively low toxicity profile and antiproliferative activities.
In colorectal cancer, the current experience is mainly experimental but promising. Histone deacetylase inhibitors are currently being
admitted as monotherapy or combination therapy either with the conventional chemotherapy or with other agents. Valproic acid
combined with ionization may enhance tumor response. Vorinostat was the first drug of this group used in clinical trial in combination
with conventional chemotherapy and managed to stabilize advanced colorectal cancer. Experimental results show that combination
therapy of vorinostat and decitabine (DNA methyl transferase inhibitor) may have optimal results. However, patients with colorectal
cancer need to be recruited in randomized clinical trials in order to evaluate the potential efficiency of these agents.
Keywords: Acetylation, clinical trials, colorectal cancer, colorectal cell lines, epigenetic changes, histone deacetylase inhibitors.
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