Despite this, attempts to therapeutically target EGFR and EGFRvIII with single agents have largely failed in patients,10 even when the drug (e.g., gefitinib) reaches high enough concentrations within the tumor.11 This study raises the possibility that resistance to EGFR-targeted therapeutics could be mediated by EGFR- and/or EGFRvIII-independent OSMR signaling. Here, EGFR is linked to neoplasm.