Figure 1.

Ionizing radiation in combination with c-MET or NOTCH inhibitors prevents tumor recurrence. (A) Treating GBM with IR reduces tumor volume, but radioresistant GICs remain. IR promotes activation of the pro-survival pathways NOTCH and c-MET in GICs, leading to tumor recurrence. (B) Single treatment of GBM tumors with either gamma secretase inhibitors (GSIs) to target NOTCH or tyrosine kinase inhibitors (TKIs) to target c-MET would kill GICs specifically and have a minor effect on tumor volume. (C) Combinatorial treatment of GSIs or TKIs with IR would target both GICs and non-GICs and prevent tumor recurrence.