Antitumor activity of a novel EGFR tyrosine kinase inhibitor against human lung carcinoma in vitro and in vivo.

Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has led to dramatic clinical improvement in selected patients with non-small cell lung cancer (NSCLC). However, intrinsic and acquired resistance to EGFR-TKI remains a common phenomenon. Novel EGFR-TKI, structurally different with erlotinib or gefitinib might be beneficial for patients with NSCLC. In this study, we examined the antitumor effect of a newly synthesized novel EGFR tyrosine kinase inhibitor (Zhao260054). In vitro studies in a panel of four different human lung cancer cell lines revealed that Zhao260054 inhibited cell proliferation with high potency and induced G(0)/G(1) arrest of cell cycle and apoptosis. Zhao260054 markedly reduced phosphorylation of EGFR and inhibited activation of ERK1/2 and AKT. Oral administration of Zhao260054 (200 mg/kg/day) to BALB/c nude mice bearing SPC-A1 xenografts significantly retarded tumor growth. In conclusion, Zhao260054 has potent antitumor activity on human lung cancer in vitro and in vivo.