Histones and lung cancer: are the histone deacetylases a promising therapeutic target?

• Published in: Cancer chemotherapy and pharmacology 2013-11, Vol.72 (5), p.935-952
• Main Authors: Petta, Vasiliki, Gkiozos, Ioannis, Strimpakos, Alex, Syrigos, Konstantinos
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cancer Research; Clinical Trials, Phase III as Topic; Drug Evaluation, Preclinical; Epigenesis, Genetic - drug effects; Histone Deacetylase Inhibitors - adverse effects; Histone Deacetylase Inhibitors - therapeutic use; Histone Deacetylases - chemistry; Histone Deacetylases - metabolism; Histones - metabolism; Humans; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Lung Neoplasms - metabolism; Medical sciences; Medicine; Medicine & Public Health; Molecular Targeted Therapy - adverse effects; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Proteins - antagonists & inhibitors; Neoplasm Proteins - metabolism; Oncology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pneumology; Randomized Controlled Trials as Topic; Reproducibility of Results; Review Article; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-013-2223-9

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.