Opinion Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jul 26, 2021; 13(7): 670-684
Published online Jul 26, 2021. doi: 10.4252/wjsc.v13.i7.670
Epigenetic modulators for brain cancer stem cells: Implications for anticancer treatment
Luana Abballe, Evelina Miele
Luana Abballe, Evelina Miele, Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome 00165, Italy
Author contributions: Abballe L collected the data and wrote the paper; Miele E contributed to the conception and design and was responsible for review supervision; both authors read and approved the final version of the manuscript.
Supported by Italian Ministry of Health, Ricerca Finalizzata, No. GR-2018-12367328 (to Miele E).
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Evelina Miele, MD, PhD, Medical Assistant, Postdoc, Research Scientist, Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Piazza di Sant'Onofrio, 4, Rome 00165, Italy. evelina.miele@opbg.net
Received: March 13, 2021
Peer-review started: March 13, 2021
First decision: April 6, 2021
Revised: April 26, 2021
Accepted: June 22, 2021
Article in press: June 22, 2021
Published online: July 26, 2021
Processing time: 131 Days and 16.1 Hours
Abstract

Primary malignant brain tumors are a major cause of morbidity and mortality in both adults and children, with a dismal prognosis despite multimodal therapeutic approaches. In the last years, a specific subpopulation of cells within the tumor bulk, named cancer stem cells (CSCs) or tumor-initiating cells, have been identified in brain tumors as responsible for cancer growth and disease progression. Stemness features of tumor cells strongly affect treatment response, leading to the escape from conventional therapeutic approaches and subsequently causing tumor relapse. Recent research efforts have focused at identifying new therapeutic strategies capable of specifically targeting CSCs in cancers by taking into consideration their complex nature. Aberrant epigenetic machinery plays a key role in the genesis and progression of brain tumors as well as inducing CSC reprogramming and preserving CSC characteristics. Thus, reverting the cancer epigenome can be considered a promising therapeutic strategy. Three main epigenetic mechanisms have been described: DNA methylation, histone modifications, and non-coding RNA, particularly microRNAs. Each of these mechanisms has been proven to be targetable by chemical compounds, known as epigenetic-based drugs or epidrugs, that specifically target epigenetic marks. We review here recent advances in the study of epigenetic modulators promoting and sustaining brain tumor stem-like cells. We focus on their potential role in cancer therapy.

Keywords: Cancer stem cells; Epigenetics; Brain tumors; Epigenetic drugs; Histone deacetylase inhibitors; DNA methyltransferase inhibitors

Core Tip: Cancer stem cells (CSCs) are characterized by an altered epigenome that contributes to treatment failure and tumor relapse. Physicians are looking for new therapeutic approaches to target specifically CSCs in cancers. In this review, we summarize literature data about epigenetic markers in brain CSCs and shed light on new epigenetic therapies.