Description:

Epidermal growth factor receptor (EGFR) is a cell-surface receptor with intrinsic intracellular protein-tyrosine kinase (TK) activity. Ligand binding induces EGFR dimerization and phosphorylation, leading to the activation of EGFR signaling pathway. In several malignancies such as non-small cell lung cancer (NSCLC), EGFR signaling is deregulated due to mutations in EGFR, which results in uncontrolled proliferation and migration of tumor cells. EGFR mutations can lead to “oncogene-addicted” cancers, where the tumor cells depend on the mutated EGFR for cell survival and malignant phenotype.  One of the most common EGFR mutations found in human patients is L858R substitution in exon 21, within the activation loop of EGFR. Patients with this mutation are sensitive to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib or erlotinib, whereas patients with wild type EGFR are not sensitive to TKI. Another clinically relevant mutation associated with acquired gefitinib and erlotinib resistance is T790M, found in exon 20. Cells expressing EGFR with both L858R and T790M mutations are resistant to induced apoptosis in the presence of gefitinib or erlotinib. 

Data:

Dose-dependent growth inhibition of BaF3 cells harboring EGFR exon 20 insertion D770-N771insSVD mutation (EL-008), control Ba/F3 cell line (EL-001) and EGFR exon 20, A767-dupASV mutation (EL-010). The cells were treated with the indicated dose of erlotinib for 72 hours and cell viability was measured using Signosis CVC reagent.