Improving the radiosensitivity of radioresistant and hypoxic glioblastoma.
In spite of increasing attention on targeted therapeutics in the treatment of glioblastoma multiforme, radiation therapy remains the most clinically effective treatment modality. However, radiotherapy only offers palliation, with hypoxia representing a major mechanism of tumor resistance. Traditional strategies to overcome the therapeutic barrier to irradiation imposed by tumor tissue hypoxia consist of improving tumor oxygenation and administering agents that increase the tumor cell sensitivity to irradiation (radiosensitizers). There is also increasing evidence that tumor tissue is composed of diverse populations of cells with heterogeneous sensitivities to irradiation. The radioresistant tumor-initiating CD133-positive glioblastoma cancer stem cells are preferentially expanded in hypoxic conditions. Therefore, identifying therapies that can specifically target the glioblastoma cancer stem cells will lead to more durable responses to radiation therapy.
Department of Neurological Surgery, University of Virginia, School of Medicine, VA, USA.
Jason P
JP
Sheehan
Mark E
ME
Shaffrey
Brinda
B
Gupta
James
J
Larner
Jeremy N
JN
Rich
Deric M
DM
Park
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D015687:Cell Hypoxia / Q000502:physiology* / Q000528:radiation effects; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D011836:Radiation Tolerance / Q000502:physiology*