Histone Deacetylase Inhibitors and Colorectal Cancer: what is new?

Author(s):

Athanasios Tampakis, Ekaterini C. Tampaki, Christian A. Nebiker and Gregory Kouraklis   Pages 1220 - 1227 ( 8 )

Abstract:

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.

Affiliation:

, , , Department of General Surgery, University Hospital of Basel, Basel, Switzerland.

Graphical Abstract:

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