Failure of Inositol Trispyrophosphate to Enhance Highly Effective Radiotherapy of GL261 Glioblastoma in Mice.
Inositol trispyrophosphate (ITPP), reported to cure hepatomas in a preclinical rat model and to have beneficial effects in several other solid tumor models, is currently in clinical trial for liver cancer. We investigated whether aggressive glioblastomas could be effectively treated with ITPP alone or in combination with radiation therapy (RT).



C57Bl/6 mice were intracranially injected with syngeneic GL261 glioblastoma cells and treated with hypofractionated radiation (5 Gy × 3), ITPP, or both. Tumors were followed by imaging, and mice sacrificed due to morbidity or at 90 days, with microscopic examination of brain sections.



RT alone significantly prolonged survival, whereas ITPP alone did not. Surprisingly, ITPP appeared to reduce the effectiveness of RT when added in combination.



ITPP was ineffective as monotherapy for glioblastoma and appeared to interfere with the beneficial impact of RT.
Jurist Center for Research, Hackensack University Medical Center, Hackensack, NJ, U.S.A.
Sujatha
S
Iyengar
Jurist Center for Research, Hackensack University Medical Center, Hackensack, NJ, U.S.A. dschwart@fastmail.fm.
David
D
Schwartz
D000818:Animals; D001835:Body Weight; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D000860:Hypoxia; D007295:Inositol Phosphates / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011878:Radiotherapy / Q000379:methods*; D016896:Treatment Outcome
D007295:Inositol Phosphates; C516441:inositol trispyrophosphate; D019869:Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
GL261; Glioblastoma; PI3K/AKT; PTEN; hypofractionated radiation; hypoxia; inositol trispyrophosphate