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

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

doi:10.3389/fcell.2020.00546

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

Front Cell Dev Biol. 2020 Jul 10:8:546. doi: 10.3389/fcell.2020.00546. eCollection 2020.

Authors

Alexandre Perla^{1

2}, Lívia Fratini^{1

2}, Paula S Cardoso^{1

2}, Carolina Nör^{3

4}, André T Brunetto^{1

5}, Algemir L Brunetto^{1

5}, Caroline Brunetto de Farias^{1

5}, Mariane Jaeger^{1

5}, Rafael Roesler^{1

2}

Affiliations

¹ Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
² Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
³ The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada.
⁴ Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada.
⁵ Children's Cancer Institute, Porto Alegre, Brazil.

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.

Keywords: brain tumor; ependymoma; epigenetics; glioma; histone deacetylase inhibitors; medulloblastoma.

Publication types

Review