Previous attempts to inhibit EGFRvIII and glioblastoma in general with both first- and second-generation TKIs and monoclonal antibodies have been relatively unsuccessful, potentially due to the lack of TKI-sensitizing mutations present in NSCLC, the additional obstacle presented by the blood-brain-barrier, and only partial effectiveness of EGFR-targeting antibodies in blocking EGFRvIII (126–129). This evidence concerns the gene EGFR and glioblastoma.