Cancer Chemotherapy and Pharmacology

, Volume 72, Issue 5, pp 935–952 | Cite as

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

  • Vasiliki Petta
  • Ioannis Gkiozos
  • Alex Strimpakos
  • Konstantinos Syrigos
Review Article
First Online:
Received:
Accepted:

Abstract

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.

Keywords

Anticancer agents Epigenetic events Histone deacetylase inhibitors Lung cancer 

Abbreviations

HAT

Histone acetyltransferase

HDAC

Histone deacetylase

HDACIs

Histone deacetylase inhibitors

TKIs

Tyrosine kinase inhibitors

NF-kB

Nuclear factor kB

COX

Cyclooxygenase

HIF-1α

Hypoxia-inducible factor-1-alpha

VEGF

Vascular endothelial growth factor

EGFR

Endothelial growth factor receptor

TRAIL

Tumor necrosis factor-related apoptosis inducing ligand

IGFBP

Insulin-like growth factor binding protein

VPA

Valproic acid

NaB

Sodium butyrate

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Notes

Conflict of interest

None.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Vasiliki Petta
    • 1
  • Ioannis Gkiozos
    • 1
  • Alex Strimpakos
    • 1
  • Konstantinos Syrigos
    • 1
    • 2
  1. 1.Oncology Unit, Third Department of Internal Medicine, Sotiria General HospitalAthens University School of MedicineAthensGreece
  2. 2.Yale School of MedicineNew HavenUSA

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