Histone Deacetylases and Histone Deacetylase Inhibitors in Neuroblastoma

Histone deacetylases (HDACs) are enzymes that play a key role in regulating gene expression by remodelling chromatin structure. An imbalance of histone acetylation caused by deregulated HDAC expression and activity is known to promote tumour progression in a number of tumour types, including neuroblastoma, the most common solid tumour 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 tumour 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 use in the clinic to treat patients with neuroblastoma.