Low Dose Ionizing Radiation Responses and Knockdown of ATM Kinase Activity in Glioma Stem Cells

Genesis of new cells in the mammalian brain has previously been regarded as a negligible event; an assumption that long limited our under-handing in the development of neoplasias. The recent discovery of perpetual lineages derived from neural stem cells has resulted in a new approach to studying the cellular behaviour of potential cancer stem cells in the brain. Glloblastoma multiforme (GBM), the most aggressive and lethal brain tumour is derived froma group of cancerous stem cells known as glioma stem cells. GBM cells are impervious to conventional therapies such as surgical resection and ionizing radiation because of their pluripotent and radioresistant properties. Thusinour study, we aim to investigate whether a combination of chemo- and radio- therapies is an effective treatment for glioma stem cells. The study utilizes a spedfic kinase inhibitor (ATMi) of the ATM (Ataxia-telangiectasia mutated) protein which is an essential protein in DNA-damage responses. In the presence of both low dose radiation and ATMi, glioma stem cells have rapid onset of cell death and reduction in growth. Since DNA damage can be inherited through cell division, accumulated DNA breaks in later generations may also lead to cell death. The limitation of conventional radiation theapy is that administration of fractionated (low) doses to reduce any potential harm to the surr ounding healthy cells in the brain out-weighs the benefits of high radiation doses to induce actual arrest in the propagation of malignant cells. Our studydemonstrates a benefit in usng low dose radiation combined with chemotherapy resulting in a reduction in malignancy of glioma stem cells.