phd program n090/n094 vascular biology june 2008 inhibition of angiogenesis vegf / vegfr inhibitors...
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PhD program N090/N094
Vascular BiologyJune 2008
Inhibition of angiogenesis
VEGF / VEGFR inhibitors
Erhard Hofer
Department of Vascular Biology and Thrombosis ResearchCenter for Biomolecular Medicine and PharmacologyMedical University of Vienna
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Figure 13.49 The Biology of Cancer (© Garland Science 2007)
Heterotypic interactions as targets for therapeutic intervention
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Inhibition of tumor angiogenesis
1-Bevacizumab 2-VEGF-trap
3-Pegaptinib
(Combination with 5-fluorouracil forcolorectal cancer)
(Macular degeneration)
4
5- SU11248 Bay43-9006
6- downstream Signals ?
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Inhibition of angiogenesis
inhibition of VEGF and VEGF signalingmAb-based
Anti-VEGF- Avastinanti-VEGFR
VEGF traptyrosine kinase inhibitors
Tumor:normalization of tumor vesselscombination therapy
Macular degeneration
Prospects for vascular tumor targetingand gene therapy
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Avastin
(Bevacizumab)
Genentech Inc.
Effects on ATCC
tumor cell lines
rhabdomyosarcoma
glioblastoma leiommyosarcoma
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Renal cell cancerPhase II trialSingle agent
Based on this phase IIIStudiesIFN-a + BevacizumabIs conductedIn renal cancer
Side effects:FeverHypertensionproteinurea
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BevacizumabColorectal cancerPhase IIICombination therapy
Hurwitz et al. 2004Mass et al. 2004
IFL: Irinotecan5-fluorouracilleucovorin
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Kabbinavar et al., 2005
5-fluorouracilleucovorin
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DC101 - VEGFR2 mAb
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AZD21771 - Astra Zeneca - preclinical
ATP-competitiveVEGFR2 kinase inhibitor,Mimics binding ofATP adenine ring
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SU11248 - Sunitinib - Pfitzer
GIST (gastrointestinal stromal tumorsKidney cancerApproved 2006
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Vascular tumor targeting
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Gentherapien:
rAdenovirenrRetroviren
Targeting of viruses to tumors, tumor endothelium
Targeting of liposomes to tumors, tumor endothelium
Oncolytic viruses
BM progenitor cells home to tumor vasculature
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