Potential Epigenetic-Based Therapeutic Targets for Glioma.

Lanlan Zang,Shukkoor Muhammed Kondengaden,Xueyuan Heng,Fengyuan Che,Lijuan Wang

doi:10.3389/fnmol.2018.00408

Lanlan Zang, Shukkoor Muhammed Kondengaden + Show 3 more

Open Access

https://doi.org/10.3389/fnmol.2018.00408

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Abstract

Glioma is characterized by a high recurrence rate, short survival times, high rates of mortality and treatment difficulties. Surgery, chemotherapy and radiation (RT) are the standard treatments, but outcomes rarely improve even after treatment. With the advancement of molecular pathology, recent studies have found that the development of glioma is closely related to various epigenetic phenomena, including DNA methylation, abnormal microRNA (miRNA), chromatin remodeling and histone modifications. Owing to the reversibility of epigenetic modifications, the proteins and genes that regulate these changes have become new targets in the treatment of glioma. In this review, we present a summary of the potential therapeutic targets of glioma and related effective treating drugs from the four aspects mentioned above. We further illustrate how epigenetic mechanisms dynamically regulate the pathogenesis and discuss the challenges of glioma treatment. Currently, among the epigenetic treatments, DNA methyltransferase (DNMT) inhibitors and histone deacetylase inhibitors (HDACIs) can be used for the treatment of tumors, either individually or in combination. In the treatment of glioma, only HDACIs remain a good option and they provide new directions for the treatment. Due to the complicated pathogenesis of glioma, epigenetic applications to glioma clinical treatment are still limited.

Highlights

Glioma is the most common form of primary malignant brain tumors, accounting for nearly 30% of all brain tumors, and one of the most lethal (Chien et al, 2016)
This review summarizes the potential epigenetic-based therapeutic targets and related drugs for glioma
Histone methyltransferases G9a, EZH2, MLL1 and MLL2 (Chang et al, 2009; Cheung et al, 2012; Liu F. et al, 2013; Kondengaden et al, 2016; Wiese et al, 2016; Banasavadi-Siddegowda et al, 2018) regulated the methylation level of lysine located in histone (Table 3); these modifications were closely related to gene transcription regulation and genome integration (Heddleston et al, 2012; Zhou et al, 2016)

Summary

Introduction

Glioma is the most common form of primary malignant brain tumors, accounting for nearly 30% of all brain tumors, and one of the most lethal (Chien et al, 2016). Multiple enzymes and genes that regulate the epigenetic modifications have become new targets for glioma treatments but for the treatment of other cancers as well.

Results

Conclusion