By Andrew D Shaw; et al

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These data strongly suggested that optimal combination therapy occurred in tumors that were positive for the respective growth factor receptors and secreted the ligand (which upregulated the receptor on tumor-associated endothelium, thus being vulnerable to TKI-mediated apoptosis). This dual targeting is not limited to EGF-R inhibition. C. Blockade of Vascular Endothelial Growth Factor Receptor Signaling Using a mouse-specific antibody (DC101) against the VEGF receptor, Bruns et al. (89) demonstrated inhibition of tumor growth, decrease in metastasis, and induction of apoptosis in both tumor cells and the tumor-associated endothelium in the human 5 pancreatic tumor model in nude mice.

Fidler IJ. Regulation of neoplastic angiogenesis. J Natl Cancer Inst Monogr 2000; 28:10–14. 34. Ebhard A, Kahlert S, Goede V, Hemmerlein B, Plate KH, Augustin HG. Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies. Cancer Res 2000; 60:1388–1393. 35. Nels V, Denzer K, Drenchahn D. Pericyte involvement in capillary sprouting during angiogenesis in situ. Cell Tissue Res 1992; 270:469–474. 36. Nor JE, Polverni PJ. Role of endothelial cell survival and death signals in angiogenesis.

78. Christodoulou C, Klouvas G, Pateli A, Mellou S, Sgouros J, Skarlos DV. Prolonged administration of weekly paclitaxel and trastuzumab in patients with advanced breast cancer. Anticancer Res 2003; 23: 737–744. 79. Herbst RS, Hong WK. IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody for treatment of head and neck cancer. Semin Oncol 2002; 29: 18–30. 80. Peggs K, Mackinnon S. Imatinib mesylate—the new gold standard for treatment of chronic myeloid leukemia. New Engl J Med 2003; 348:1048–1050.

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