Brain tumor stem cells as research and treatment targets

Glioblastoma multiforme (GBM) is one of the most malignant forms of human cancer. Despite intensive treatment, the mean survival of GBM patients remains about 1 year. Recent cancer studies revealed that cancer tissues are pathologically heterogeneous and only a small population of cells has the specific ability to reinitiate cancer. This small cell population is called cancer stem cells (CSCs); in brain tumors these are known as brain tumor stem cells (BTSCs). The identification of BTSCs yielded new insights into chemo- and radioresistance, by which BTSCs can survive selectively and initiate recurrence. Research focused on BTSCs as treatment targets may contribute to the discovery of new therapeutic strategies. Clinical and basic research studies gradually led to improved outcomes in patients with brain tumors. Stupp et al. reported a mean survival of 14.6 months in glioblastoma multiforme (GBM) patients treated with radiotherapy plus temozolomide and 12.1 months in those subjected to radiotherapy alone. Earlier cancer therapies primarily targeted rapidly dividing cells but not minor populations of slowly dividing cells that contain BTSCs. Accumulating evidence suggests that BTSCs may represent an excellent tool for discovering new strategies to treat GBM patients. In this review, we present evidence supporting the CSC model of tumor progression, and discuss difficulties encountered in CSC research and experimental and therapeutic implications. (author)