ZD6474, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, inhibits growth of experimental lung metastasis and production of malignant pleural effusions in a non-small cell lung cancer model.

摘要: ZD6474 is a novel, orally active inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, with some additional activity against epidermal receptor (EGFR) kinase. The purpose this study was to determine the potential in control established experimental lung metastasis and pleural effusions produced by human non-small cell cancer (NSCLC) cells. PC14PE6 (adenocarcinoma) H226 (squamous carcinoma) cells express high levels EGFR only overexpress VEGF. Neither nor kinase gefitinib inhibit proliferation or vitro. Both inoculated intravenously into nude mice induced multiple nodules after 5-7 weeks. In addition, bloody effusions. Daily oral treatment did not reduce number cells, but weight size nodules. also inhibited production Histological analyses lesions revealed that activation VEGFR-2 reduced tumor vascularization proliferation. Therapeutic effects were considered likely be due inhibition because inactive model. These results indicate ZD6474, an VEGFR-2, may useful controlling NSCLC.