Improving the radiosensitivity of radioresistant and hypoxic glioblastoma

Author:

Sheehan Jason P1,Shaffrey Mark E1,Gupta Brinda1,Larner James2,Rich Jeremy N3,Park Deric M

Affiliation:

1. Department of Neurological Surgery, University of Virginia, School of Medicine, VA, USA

2. Department of Radiation Oncology, University of Virginia, School of Medicine, VA, USA

3. Department of Stem Cell Biology & Regenerative Medicine, Cleveland Clinic, VA, USA

Abstract

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.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Oncology,General Medicine

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