Ph D program N 090N 094 Vascular Biology
Ph. D program N 090/N 094 Vascular Biology June 2008 Inhibition of angiogenesis VEGF / VEGFR inhibitors Erhard Hofer Department of Vascular Biology and Thrombosis Research Center for Biomolecular Medicine and Pharmacology Medical University of Vienna
Heterotypic interactions as targets for therapeutic intervention Figure 13. 49 The Biology of Cancer (© Garland Science 2007)
Inhibition of tumor angiogenesis (Combination with 5 -fluorouracil for colorectal cancer) 1 -Bevacizumab 2 -VEGF-trap 3 -Pegaptinib (Macular degeneration) 4 6 - downstream Signals ? 5 - SU 11248 Bay 43 -9006
Inhibition of angiogenesis inhibition of VEGF and VEGF signaling m. Ab-based Anti-VEGF- Avastin anti-VEGFR VEGF trap tyrosine kinase inhibitors Tumor: normalization of tumor vessels combination therapy Macular degeneration Prospects for vascular tumor targeting and gene therapy
rhabdomyosarcoma Avastin (Bevacizumab) Genentech Inc. glioblastoma Effects on ATCC tumor cell lines leiommyosarcoma
Renal cell cancer Phase II trial Single agent Based on this phase III Studies IFN-a + Bevacizumab Is conducted In renal cancer Side effects: Fever Hypertension proteinurea
Bevacizumab Colorectal cancer Phase III Combination therapy Hurwitz et al. 2004 Mass et al. 2004 IFL: Irinotecan 5 -fluorouracil leucovorin
Kabbinavar et al. , 2005 5 -fluorouracil leucovorin
DC 101 - VEGFR 2 m. Ab
AZD 21771 - Astra Zeneca - preclinical ATP-competitive VEGFR 2 kinase inhibitor, Mimics binding of ATP adenine ring
SU 11248 - Sunitinib - Pfitzer GIST (gastrointestinal stromal tumors Kidney cancer Approved 2006
Vascular tumor targeting
Gentherapien: r. Adenoviren r. Retroviren 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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