Key actors in cancer therapy: epigenetic modifiers

Remzi Okan Akar,Nazlıhan Aztopal,Selin Selvi̇,Engin Ulukaya

doi:10.3906/biy-1903-39

Abstract

Epigenetic reprogramming plays a crucial role in the tumorigenicity and maintenance of tumor-specific gene expression that especially occurs through DNA methylation and/or histone modifications. It has well-defined mechanisms. It is known that alterations in the DNA methylation pattern and/or the loss of specific histone acetylation/methylation markers are related to several hallmarks of cancer, such as drug resistance, stemness, epithelial-mesenchymal transition, and metastasis. It has also recently been highlighted that epigenetic alterations are critical for the regulation of the stemlike properties of cancer cells (tumor-initiating cells; cancer stem cells). Cancer stem cells are thought to be responsible for the recurrence of cancer which makes the patient return to the clinic with metastatic tumor tissue. Hence, the dysregulation of epigenetic machinery represents potential new therapeutic targets. Therefore, compounds with epigenetic activities have become crucial for developing new therapy regimens (e.g., antimetastatic agents) in the fight against cancer. Here, we review the epigenetic modifiers that have already been used in the clinic and/or in clinical trials, related preclinical studies in cancer therapy, and the smart combination strategies that target cancer stem cells along with the other cancer cells. The emerging role of epitranscriptome (RNA epigenetic) in cancer therapy has also been included in this review as a new avenue and potential target for the better management of cancer-beneficial epigenetic machinery.

Highlights

Success in cancer treatment is still not satisfactory, new chemotherapeutics have recently been introduced in the clinic
It has been shown that cancer stem cells (CSCs) are resistant to treatment and that they play a crucial role in recurrence (Easwaran et al, 2014; Toh et al, 2017)
The current review aims to address the following questions: i) How does epigenetic machinery contribute to tumor growth and progression? ii) What are the current clinical and preclinical studies on the usage of epigenetic modifiers in cancer therapy? iii) What are the benefits of using these modifiers to target CSCs? iv) How can combinatorial therapy be effectively used to target/

Summary

Introduction

Success in cancer treatment is still not satisfactory, new chemotherapeutics have recently been introduced in the clinic. Discovered inhibitors have been introduced in addition to DNMT and HDAC inhibitors, such as bromodomain and extraterminal protein (BET), histone methyltransferase (HMT), protein arginine methyltransferase (PRMT), and lysine-specific demethylase 1A (LSD1/KDM1A) inhibitors, which are able to target different epigenetic mechanisms (Jones et al, 2016). It has been shown in these studies that epigenetic drugs (epidrugs) have promising results for the treatment of cancer. Overview of the hot top epigenetic alterations in normal cells, cancer, and CSCs

Effective chemotherapeutic option for osteosarcoma treatment

Findings

Conclusion