Abstract 3370: DNA repair in glioma stem cell-mediated radiation resistance

Abstract

Abstract Glioblastoma multiforme is the most common type of primary brain cancer in adults and has a 14-month median survival after diagnosis. This low survival is due to resistance to the currently available therapies, which include surgery, radiation, chemotherapy, and anti-angiogenic drugs. Resistance to chemotherapy and radiation in these tumors has been linked to a subgroup of highly tumorigenic cells, called glioblastoma stem cells (GSCs), that resemble normal neural progenitor cells. GSCs have the ability to self-renew, differentiate into various lineages, and re-propagate the tumor, making GSCs an attractive target for treatment. Radiation-treated GSCs retain their tumorigenic capacity and have decreased apoptosis compared to non-GSCs. In addition, GSCs have enhanced DNA damage response activation and faster DNA double-stranded break (DSB) resolution relative to non-GSCs after exposure to ionizing radiation (IR). Exposure to low dose radiation induces DSBs, which are repaired by either non-homologous end joining (NHEJ) or homologous recombination (HR). Targeting key proteins involved in HR, such as RAD51, has been shown to reduce glioma cell viability. We are investigating the molecular mechanisms by which DNA repair mediates radiation resistance in GSCs, with some lead candidates identified. Based on a DNA repair gene array, several candidates were identified to be preferentially expressed in GSCs. Current work is focusing on targeting these genes and elucidating their role in radiation resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3370. doi:1538-7445.AM2012-3370