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Dr. David Nathanson and his team at UCLA are developing an EGFR-targeted drug for glioblastoma (GBM) called KTM-101. About half of GBMs have EGFR alterations, so there have been many attempts to target EGFR, but EGFR-targeted monotherapies have repeatedly disappointed in GBM. Several likely reasons for these failures include poor blood-brain barrier penetration, the heterogeneity and adaptability of GBM tumors, and the ability of tumors to bypass a single blocked pathway or even lose the targeted EGFR alteration over time. We will be watching KTM-101 for further validation in larger studies, and we hope to see EGFR-targeted therapy increasingly explored as one component of rational combination approaches rather than as a stand-alone strategy.