to WTiNPCs (Supplementary Fig. 9d,e). Treatment with the identified compounds significantly compromised the self-renewal properties of Ras/EGFR/SrciNPCs and p53KD-Ras/EGFR/SrciNPCs (Fig. 4c). In addition, iNPC-differentiated neural cells demonstrated higher susceptibility to chemical treatments (Supplementary Fig. 10a). Next, we investigated the effect of the identified compounds in established glioma lines. Treatment of U-87 MG and LN229 glioma cells with the different compounds demonstrated the efficient induction of cell death with nelarabine and letrozole, whereas capecitabine was largely ineffective (Supplementary Fig. 10b). Last, we decided to test the effect of the identified compounds alongside metabolic modulators in a more physiological setting. To this end, we relied on the use of ex vivo organotypic brain slices563839. Injection of primary GTICs into 300 μm brain slices resulted in the formation of well-defined tumour masses in less than 8 days (Fig. 4d). Treatment of brain slices indicated a specific effect against primary GTIC tumours with 2-DG, nelarabine and letrozole, demonstrating the highest anti-tumour potential (Fig. 4d,e).
