The anti-vascular and anti-tumor response of human lung cancer growing orthotopically in mice to AEE788, a tyrosine kinase inhibitor of EGFR and VEGFR, is dependent upon EGF/TGFα expression

摘要: 3031 Introduction: Targeting of EGFR has been extensively studied in lung cancer; yet, clinical data show that only a fraction patients can respond to inhibitors. The development and validation strategies identify likely benefit from these agents is therefore critical importance. We hypothesized the expression EGF/TGFα by tumors needed for activation both tumor (autocrine) tumor-associated endothelial (paracrine) cells would thus be required an anti-tumor anti-vascular response signal blockade. Methods: human adenocarcinoma cell lines NCIH441 (EGF/TGFα+/EGFR+) PC14PE6 (EGF/TGFα-/EGFR+) were injected into lungs mice. Once formed, mice randomized treatment with AEE788 or vehicle. When control became moribund, animals killed assessed size, pleural effusion, metastasis, immunohistochemical studies. nucleotide sequence was analyzed H441 lines. Results: found wild type cells. Treatment bearing resulted significant (p