Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors
Function-blocking antibodies to VEGF receptors R1 and R2 were used to probe their roles in controlling angiogenesis in a mouse model of pancreatic islet carcinogenesis. Inhibition of VEGFR2 but not VEGFR1 markedly disrupted angiogenic switching, persistent angiogenesis, and initial tumor growth. In...
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| Veröffentlicht in: | Cancer cell 2005-10, Vol.8 (4), p.299-309 |
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| creator | Casanovas, Oriol Hicklin, Daniel J. Bergers, Gabriele Hanahan, Douglas |
| description | Function-blocking antibodies to VEGF receptors R1 and R2 were used to probe their roles in controlling angiogenesis in a mouse model of pancreatic islet carcinogenesis. Inhibition of VEGFR2 but not VEGFR1 markedly disrupted angiogenic switching, persistent angiogenesis, and initial tumor growth. In late-stage tumors, phenotypic resistance to VEGFR2 blockade emerged, as tumors regrew during treatment after an initial period of growth suppression. This resistance to VEGF blockade involves reactivation of tumor angiogenesis, independent of VEGF and associated with hypoxia-mediated induction of other proangiogenic factors, including members of the FGF family. These other proangiogenic signals are functionally implicated in the revascularization and regrowth of tumors in the evasion phase, as FGF blockade impairs progression in the face of VEGF inhibition. |
| doi_str_mv | 10.1016/j.ccr.2005.09.005 |
| format | Article |
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| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals |
| subjects | Cell Line, Tumor Drug Resistance, Neoplasm Fibroblast Growth Factors - antagonists & inhibitors Fibroblast Growth Factors - metabolism Humans Islets of Langerhans - pathology Neovascularization, Pathologic - prevention & control Pancreatic Neoplasms - blood supply Pancreatic Neoplasms - metabolism Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors Signal Transduction - physiology Vascular Endothelial Growth Factor A - antagonists & inhibitors Vascular Endothelial Growth Factor A - physiology |
| title | Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors |
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