Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential.

Alexandre Perla,Carolina Nör,Paula S Cardoso,Mariane Jaeger,Rafael Roesler,André T Brunetto,Algemir L Brunetto,Caroline Brunetto De Farias,Lívia Fratini

doi:10.3389/fcell.2020.00546

Abstract

Brain cancers are the leading cause of cancer-related deaths in children. Biological changes in these tumors likely include epigenetic deregulation during embryonal development of the nervous system. Histone acetylation is one of the most widely investigated epigenetic processes, and histone deacetylase inhibitors (HDACis) are increasingly important candidate treatments in many cancer types. Here, we review advances in our understanding of how HDACis display antitumor effects in experimental models of specific pediatric brain tumor types, i.e., medulloblastoma (MB), ependymoma (EPN), pediatric high-grade gliomas (HGGs), and rhabdoid and atypical teratoid/rhabdoid tumors (ATRTs). We also discuss clinical perspectives for the use of HDACis in the treatment of pediatric brain tumors.

Highlights

Brain tumors of the childhood represent the leading cause of cancer-related deaths in children aged 0–14 years, and survivors often present long-term neurological sequelae that impair their quality of life (Ostrom et al, 2016)
Some HDAC inhibitors (HDACis) have already been approved by the United States Food and Drug Administration (FDA) for the treatment of other cancer types (i.e., SAHA and romidepsin for the treatment of cutaneous T-cell lymphoma and belinostat and panobinostat for the treatment of peripheral T-cell lymphoma and multiple myeloma, respectively)
Given the increasingly promising role of drug repurposing or repositioning in the identification of potential novel therapeutic strategies for pediatric brain tumors (Bahmad et al, 2020), those agents could be tested in clinical trials of patients with these cancer types

Summary

Introduction

Brain tumors of the childhood represent the leading cause of cancer-related deaths in children aged 0–14 years, and survivors often present long-term neurological sequelae that impair their quality of life (Ostrom et al, 2016). A variety of HDACis, including MS-275, SAHA, TSA, and VPA, are able to inhibit proliferation of MB cell lines and induce histone H4 hyperacetylation, reactivation of expression of growth regulatory genes, and induction of apoptosis, as well as reduction of MB xenograft growth in vivo (Furchert et al, 2007).

Results

Conclusion