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.
We searched reviews and original papers in Pubmed over the last 10
years.
We identified 76 original papers on this topic.
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
