Differential responses of tumors and normal brain to the combined treatment of 2-DG and radiation in glioablastoma.
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.
Prasanna
Venkatesh K
VK
Manipal Institute for Neurological Disorders, Bangalore, India.
Venkataramana
Neelam K
NK
Dwarakanath
B S
BS
Santhosh
Vani
V
D000328:Adult; D000368:Aged; D001921:Brain / Q000187:drug effects / Q000528:radiation effects; D001932:Brain Neoplasms / Q000628:therapy*; D003131:Combined Modality Therapy; D003847:Deoxyglucose / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011878:Radiotherapy
D011838:Radiation-Sensitizing Agents; D003847:Deoxyglucose