DNA Repair mechanisms in glioblastoma cancer stem cells

Glioblastomas remain the most common and deadly adult brain tumor despite numerous advances made in the understanding of tumor biology. One such advance is the recent appreciation for a cellular hierarchy within the tumor bulk with only a subpopulation of cells, termed cancer stem cells, able to reinitiate tumor growth in transplantation assays. With the identification of these cells comes a further complexity in our consideration of how the heterogeneous cell populations within the tumor respond to therapeutic intervention. Cancer stem cells within glioblastomas, or glioma stem cells (GSCs), have been reported to have a chemo- and radioresistance phenotype as compared to the non-stem cell population. This is critical for patient care as radiotherapy and chemotherapy with the DNA alkylating agent, temozolomide, are the current standards of care. Importantly, both of these treatments rely on the cellular response to DNA damage to elicit their therapeutic benefit. For GSCs, the field is just beginning to appreciate how these cells respond on a molecular level to DNA damage. Nonetheless, advances have been made that highlight novel modes of potential therapeutic intervention and underscore the requirement for further studies aimed at elucidation of this key cellular pathway in GSC biology. This chapter summarizes our current understanding of the DNA damage response in GSCs.