Jun 29, 2013

Epigenetic pathways and glioblastoma treatment

Epigenetics : Official Journal of the DNA Methylation Society
Jennifer ClarkeNagi G Ayad

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.

  • References67
  • Citations19

References

  • References67
  • Citations19

Mentioned in this Paper

Glioblastoma Multiforme
Biochemical Pathway
Neoplasm Recurrence, Local
Enzymes, antithrombotic
Immunologic Adjuvants
Adjuvant
Temozolomide, ORAL,5 MG Administered
Neoplasms
Transcription Initiation
Recurrent Malignant Neoplasm

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