Radiotherapy and Glioma Stem Cells: Searching for Chinks in Cellular Armor

Purpose of Review: Radiation became a pillar of oncologic treatment in the last century and provided a powerful and effective locoregional treatment of solid malignancies. After achieving some of the first cures in lymphomas and skin cancers, it assumed a key role in the curative treatment of epithelioid malignancies. Despite success across a variety of histologic types, glioblastoma (GBM), the most common primary brain tumor afflicting adults, remains ultimately resistant to current radiation strategies. While GBMs demonstrate an initial response, recurrence is essentially universal and fatal and typically reoccur in the areas that received the most intense radiation. Recent Findings: Glioma stem cells (GSCs), a subpopulation of tumor cells with expression profiles similar to neural stem cells and marked self-renewal capacities, have been shown to drive tumor recurrence and preclude curative radiotherapy. Recent research has shown that these cells have enhanced DNA repair capacity and elevated resistance to cytotoxic ion fluxes and escape multimodality therapies. Summary: We will analyze the current understanding of GSCs and radiation by highlighting key discoveries probing their ability to withstand radiotherapy. We then speculate on novel mechanisms by which GSC can be made sensitive to or specifically targeted by radiation therapy.