Inhibition of EGFRvIII by a tyrosine kinase inhibitor AG1478 downregulates Bcl‐XL expression and restores sensitivity of GBM cells to cisplatin 9, and this combination treatment suppresses growth of GBM xenografts overexpressing EGFRvIII 10, suggesting that targeting EGFR signaling could be a reasonable approach for high‐grade glioma therapy. Here, EGFR is linked to central nervous system cancer.