Histone Deacetylases and Histone Deacetylase Inhibitors in Neuroblastoma

Monica Phimmachanh; Jeremy Z R Han; Yolande E I O'Donnell; Sharissa L Latham; David R Croucher

doi:10.3389/fcell.2020.578770

Histone Deacetylases and Histone Deacetylase Inhibitors in Neuroblastoma

Front Cell Dev Biol. 2020 Oct 7:8:578770. doi: 10.3389/fcell.2020.578770. eCollection 2020.

Authors

Monica Phimmachanh¹, Jeremy Z R Han¹, Yolande E I O'Donnell¹, Sharissa L Latham^{1

2}, David R Croucher^{1

2}

Affiliations

¹ The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, NSW, Australia.
² St Vincent's Hospital Clinical School, University of New South Wales, Sydney, NSW, Australia.

Abstract

Histone deacetylases (HDACs) are enzymes that play a key role in regulating gene expression by remodeling chromatin structure. An imbalance of histone acetylation caused by deregulated HDAC expression and activity is known to promote tumor progression in a number of tumor types, including neuroblastoma, the most common solid tumor in children. Consequently, the inhibition of HDACs has emerged as a potential strategy to reverse these aberrant epigenetic changes, and several classes of HDAC inhibitors (HDACi) have been shown to inhibit tumor proliferation, or induce differentiation, apoptosis and cell cycle arrest in neuroblastoma. Further, the combined use of HDACi with other chemotherapy agents, or radiotherapy, has shown promising pre-clinical results and various HDACi have progressed to different stages in clinical trials. Despite this, the effects of HDACi are multifaceted and more work needs to be done to unravel their specific mechanisms of actions. In this review, we discuss the functional role of HDACs in neuroblastoma and the potential of HDACi to be optimized for development and use in the clinic for treatment of patients with neuroblastoma.

Keywords: acetylation; apoptosis; cell cycle arrest; differentiation; histone deacetylase inhibitor; histone deacetylases; neuroblastoma.

Publication types

Review