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Ref Type Journal Article
PMID (19528456)
Authors Siemann DW, Norris CM, Ryan A, Shi W
Title Impact of tumor cell VEGF expression on the in vivo efficacy of vandetanib (ZACTIMA; ZD6474).
Journal Vol Issue Date Pages Journal Short Title
Anticancer research 29 6 2009 Jun 1987-92 Anticancer Res
URL
Abstract Text VEGF is the key player in tumor angiogenesis. In the current study, the impact of VEGF expression on the response of tumors to the VEGFR2 associated tyrosine kinase inhibitor vandetanib was evaluated.Human colon carcinoma (HT29) and murine squamous carcinoma (SCCVII) clonal cell lines expressing varying levels of VEGF were established and their response to vandetanib was assessed in tissue culture and as solid tumors.Vandetanib treatment had no effect on tumor cell clonogenic cell survival in vitro but doses >or=10 nM significantly reduced endothelial cell migration. In vivo, tumors derived from cell clones expressing high levels of VEGF displayed significantly enhanced angiogenesis and more aggressive growth. An intradermal angiogenesis assay was used to demonstrate that a 4-day treatment with vandetanib (50 mg/kg/day) was able to significantly inhibit blood vessel growth induced by both parental and high VEGF-expressing tumor cell clones. In the HT29 tumor model, treatment response to vandetanib (50 mg/kg/day, Monday-Friday for 2 weeks) was greatest in xenografts derived from the highest VEGF-expressing cell clones. A similar trend was noted in the SCCVII tumor model. The present findings indicate that vandetanib therapy effectively counteracted the aggressive feature of tumor growth resulting from VEGF over-expressing tumor cells and suggest that such tumors may be particularly well suited for anti-VEGF interventions.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References