Purpose Deoxyribonucleic acid is wrapped around an
octamer of core histone proteins to form a nucleosome, the
basic structure of chromatin. Two main families of
enzymes maintain the equilibrium of acetyl groups added
to or removed from lysine residues. Histone deacetylases
(HDACs) catalyze the removal of acetyl groups from
lysine residues in histone amino termini and non-histone
proteins also, leading to chromatin condensation and
transcriptional repression. HDAC overexpression, resulting
in tumor suppressor genes silencing, has been found in
several human cancer tissues, indicating that aberrant epigenetic
activity is associated with cancer development.
Therefore, inhibitors of these enzymes are emerging anticancer
agents and there is evidence supporting their role in
hematological malignancies. The minimal efficacy of
conventional chemotherapy has prompted a renewed focus
on targeted therapy based on pathways altered during the
pathogenesis of lung cancer. We identify the pleiotropic
antitumor effects of HDAC inhibitors in lung cancer,
focusing on the result caused by their use individually, as
well as in combination with other chemotherapeutic agents,
in lung cancer cell lines and in clinical trials.
Method We searched reviews and original papers in
Pubmed over the last 10 years.
Results We identified 76 original papers on this topic.
Conclusions Numerous preclinical studies have shown
that HDAC inhibitors exhibit impressive antitumor activity
in lung cancer cell lines. Nevertheless, Phase III randomized
studies do not support HDAC inhibitors use in lung
cancer patients in everyday practice. Ongoing and future
studies would help determine their role in lung cancer
treatment.
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