The Potential Role of Histone Modifications in Glioblastoma Therapy: Review Article

Abstract

Glioblastoma (GBM) is considered the most aggressive primary brain tumor. Recurrence after treatment is a significant problem with a failed response to optimal therapies. The recurrence of GBM is linked to different cellular and molecular pathways. Not only genetics are involved in gliomagenesis, but also epigenetics. Histone modulation through acetylation, phosphorylation, ubiquitination, and methylation can regulate gene expression and may play a role in the pathogenesis of GBM. Preclinical and clinical studies currently target epigenetic enzymes in gliomas, including a new generation of histone deacetylase (HDAC) inhibitors. Herein, I tried to highlight current research in glioma epigenetics, focusing on the culprit of histone modifications and the use of HDAC target therapies as a possible treatment line for glioblastoma.

Long-read sequencing for brain tumors

“…As previously mentioned, epigenetics plays a crucial role in carcinogenesis ( 116 , 155 ). This term, which was initially introduced by Conrad Waddington in 1942 as “the branch of biology which studies the causal interactions between genes and their products, which bring the phenotype into being” ( 156 , 157 ), has been extensively studied in the recent years as there are known mechanisms that modify chromatin structure and have been reported to be crucial in various and aggressive CNS tumors such as GBM ( 158 – 160 ), medulloblastoma ( 161 – 163 ), ependymoma ( 164 , 165 ), diffuse intrinsic pontine gliomas ( 166 , 167 ), meningioma ( 147 ), among others. The epigenetic modifications that are capable of modifying chromatin structure are encompassed into four categories: DNA methylation, histone modifications, and non-covalent mechanisms (e.g., nucleosome remodeling, non-coding RNAs) ( 155 ).…”