The epigenetics of brain tumors and its modulation during radiation: A review

Life Sci. 2020 Sep 1:256:117974. doi: 10.1016/j.lfs.2020.117974. Epub 2020 Jun 15.

Abstract

The brain tumor is the abnormal growth of heterogeneous cells around the central nervous system and spinal cord. Most clinically prominent brain tumors affecting both adult and pediatric are glioblastoma, medulloblastoma, and ependymoma and they are classified according to their origin of tissue. Chemotherapy, radiotherapy, and surgery are important treatments available to date. However, these treatments fail due to multiple reasons, including chemoresistance and radiation resistance of cancer cells. Thus, there is a need of new therapeutic designs to target cell signaling and molecular events which are responsible for this resistance. Recently epigenetic changes received increased attention because it helps in understanding chromatin-mediated disease mechanism. The epigenetic modification alters chromatin structure that affects the docking site of many drugs which cause chemo-resistance of cancer therapy. This review centers the mechanism of how epigenetic changes affect the transcription repression and activation of various genes including Polycomb gene, V-Myc avian myelocytomatosis viral oncogene (MYCN). This review also put forth the pathway of radiation-induced reactive oxygen species generation and its role in epigenetic changes in the cellular level and its impact on tissue physiology. Additionally, there is a strong relationship between the behavior of an individual and environment-induced epigenetic regulation of gene expression. The review also discusses Transcriptome heterogeneity and role of tumor microenvironment in glioblastoma. Overall, this review emphasis important and novel epigenetic targets that could be of therapeutic benefit, which helps in overcoming the unsolved chromatin alteration in brain cancer.

Keywords: Epigenetics; Glioblastoma; ROS; Radiation.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / radiotherapy*
  • Epigenesis, Genetic / drug effects
  • Epigenesis, Genetic / genetics*
  • Epigenesis, Genetic / radiation effects
  • Humans
  • Radiation-Sensitizing Agents / pharmacology
  • Radiation-Sensitizing Agents / therapeutic use
  • Reactive Oxygen Species / metabolism
  • Transcriptome / drug effects
  • Transcriptome / genetics
  • Transcriptome / radiation effects
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / radiation effects

Substances

  • Radiation-Sensitizing Agents
  • Reactive Oxygen Species