Figure 3.

A model of glioblastoma stem cell (GSC)-targeted therapy. GSC have the ability to self-renew as well as give rise to new tumors. In order to prevent post-treatment tumor recurrence, a treatment targeting essential gene pathways for GSC must be incorporated into current therapeutic modalities. Several gene pathways have been determined to be required for maintaining tumorigenic capacity and a radio-chemoresistant phenotype of GSC. These signaling pathways work collaboratively and cooperatively to generate a quiescent, undifferentiated, and anti-apoptotic phenotype as well as to constitutively activate the DNA damage checkpoint response in GSC. Importantly, GSC exhibit a chemoresistant phenotype via constant activation of the DNA damage checkpoint response and AKT survival pathway, as well as expression of high levels of both anti-apoptotic proteins and drug efflux transporters. In order to eradicate a tumor, a therapeutic strategy that disrupts GSC signaling pathways must be developed to be fully integrated into radio-chemotherapy in order to target both GSC and non-GSC populations.