Tumor Cell Killing Mechanisms of Epidermal Growth Factor Receptor (EGFR) Antibodies Are Not Affected by Lung Cancer-Associated EGFR Kinase Mutations

摘要: The epidermal growth factor receptor (EGFR) serves as a molecular target for novel cancer therapeutics such tyrosine kinase inhibitors (TKI) and EGFR Abs. Recently, specific mutations in the domain of lung cancers were identified, which altered signaling capacity correlated with clinical response or resistance to TKI therapy. In present study, we investigated impact on antitumor cell activity Thus, an EGFR-responsive line model was established, cells tumor-derived (L858R, G719S, delE746-A750) significantly more sensitive than wild-type EGFR-expressing cells. A clinically relevant secondary mutation (T790M) abolished sensitivity. Significantly, effects Abs, including inhibition Ab-dependent cellular cytotoxicity, not affected by any these mutations. Somatic tumor-associated mutations, modulate TKI, therefore do therapeutic Abs vitro.