Abstract A23: HER2 levels affect sensitivity and resistance to EGFR inhibition in EGFR mutant lung cancer

摘要: EGFR mutant lung cancers eventually become resistant to treatment with tyrosine kinase inhibitors (TKIs) such as erlotinib. The combination of an irreversible TKI, afatinib, and the anti-EGFR monoclonal antibody, cetuximab, depletes both phosphorylated total can overcome resistance in mouse tumor models human patients acquired resistance. Since afatinib is also a potent HER2 inhibitor, here we investigated role cells. We show vitro vivo that plus cetuximab or related panitumumab, significantly inhibits phosphorylation. overexpression knockdown confers sensitivity, respectively, all studied cell line models. Fluorescent situ hybridization analysis revealed was amplified 3 26 (12%) tumors versus only 1 99 (1%) untreated adenocarcinomas (p=0.03 Fisher9s exact test). Notably, amplification T790M were mutually exclusive (0 17 T790M-positive 9 T790M-negative cases (p=0.02 test)). Collectively, these results reveal previously unrecognized mechanism TKIs provide rationale assess status possibly target TKIs.