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

33 Citations (Scopus)

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

Fingerprint

Glioblastoma
Epigenomics
Therapeutics
Neoplasms
temozolomide
Recurrence
Genome
Atlases
Enzymes
Drug Discovery
Adjuvant Chemotherapy
Systems Analysis
Brain Neoplasms
Radiotherapy
Survival

Keywords

  • Drug discovery
  • Epigenetics
  • Glioblastoma
  • Statistical modeling

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Cite this

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

Epigenetic pathways and glioblastoma treatment. / Clarke, Jennifer; Penas, Clara; Pastori, Chiara; Komotar, Ricardo J.; Bregy, Amade; Shah, Ashish H.; Wahlestedt, Claes; Ayad, Nagi G.

In: Epigenetics, Vol. 8, No. 8, 2013, p. 785-795.

Research output: Contribution to journalReview article

Clarke, J, Penas, C, Pastori, C, Komotar, RJ, Bregy, A, Shah, AH, Wahlestedt, C & Ayad, NG 2013, 'Epigenetic pathways and glioblastoma treatment', Epigenetics, vol. 8, no. 8, pp. 785-795. https://doi.org/10.4161/epi.25440
Clarke J, Penas C, Pastori C, Komotar RJ, Bregy A, Shah AH et al. Epigenetic pathways and glioblastoma treatment. Epigenetics. 2013;8(8):785-795. https://doi.org/10.4161/epi.25440
Clarke, Jennifer ; Penas, Clara ; Pastori, Chiara ; Komotar, Ricardo J. ; Bregy, Amade ; Shah, Ashish H. ; Wahlestedt, Claes ; Ayad, Nagi G. / Epigenetic pathways and glioblastoma treatment. In: Epigenetics. 2013 ; Vol. 8, No. 8. pp. 785-795.
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