Epigenetic pathways and glioblastoma treatment

Jennifer Clarke, Clara Penas, Chiara Pastori, Ricardo J. Komotar, Amade Bregy, Ashish H. Shah, Claes Wahlestedt, Nagi G. Ayad

Research output: Contribution to journalReview article

35 Scopus citations

Abstract

Glioblastoma multiforme (GBM) is the most common malignant adult brain tumor. Standard GBM treatment includes maximal safe surgical resection with combination radiotherapy and adjuvant temozolomide (TMZ) chemotherapy. Alarmingly, patient survival at five-years is below 10%. This is in part due to the invasive behavior of the tumor and the resulting inability to resect greater than 98% of some tumors. In fact, recurrence after such treatment may be inevitable, even in cases where gross total resection is achieved. The Cancer Genome Atlas (TCGA) research network performed whole genome sequencing of GBM tumors and found that GBM recurrence is linked to epigenetic mechanisms and pathways. Central to these pathways are epigenetic enzymes, which have recently emerged as possible new drug targets for multiple cancers, including GBM. Here we review GBM treatment, and provide a systems approach to identifying epigenetic drivers of GBM tumor progression based on temporal modeling of putative GBM cells of origin. We also discuss advances in defining epigenetic mechanisms controlling GBM initiation and recurrence and the drug discovery considerations associated with targeting epigenetic enzymes for GBM treatment.

Original languageEnglish (US)
Pages (from-to)785-795
Number of pages11
JournalEpigenetics
Volume8
Issue number8
DOIs
StatePublished - 2013

Keywords

  • Drug discovery
  • Epigenetics
  • Glioblastoma
  • Statistical modeling

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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    Clarke, J., Penas, C., Pastori, C., Komotar, R. J., Bregy, A., Shah, A. H., Wahlestedt, C., & Ayad, N. G. (2013). Epigenetic pathways and glioblastoma treatment. Epigenetics, 8(8), 785-795. https://doi.org/10.4161/epi.25440