Differential responses of tumors and normal brain to the combined treatment of 2-DG and radiation in glioablastoma

J Cancer Res Ther. 2009 Sep:5 Suppl 1:S44-7. doi: 10.4103/0973-1482.55141.

Abstract

2-Deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolysis, enhances radiation damage selectively in tumor cells by modulating damage response pathways resulting in cell death in vitro and local tumor control. Phase I and II clinical trials in patients with malignant glioma have shown excellent tolerance to a combined treatment of orally administered 2-DG and hypofractionated radiotherapy without any acute toxicity and late radiation damage. Phase III efficacy trials are currently at an advanced stage. Re-exploratory surgery performed in 13 patients due to persistent symptoms of elevated ICP and mass effect at different follow-up periods revealed extensive tumor necrosis with well-preserved normal brain tissue adjoining the tumor included in the treatment volume as revealed by a histological examination. These observations are perhaps the first clinical evidences for differential effects of 2-DG on tumors and normal tissues in conformity with earlier in vitro and in vivo studies in normal and tumor-bearing mice.

MeSH terms

  • Adult
  • Aged
  • Brain / drug effects
  • Brain / radiation effects
  • Brain Neoplasms / therapy*
  • Combined Modality Therapy
  • Deoxyglucose / therapeutic use*
  • Female
  • Glioblastoma / therapy*
  • Humans
  • Male
  • Middle Aged
  • Radiation-Sensitizing Agents / therapeutic use*
  • Radiotherapy

Substances

  • Radiation-Sensitizing Agents
  • Deoxyglucose