1. Inhibition of angiogenesis
PhD program N090/N094
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

2. Heterotypic interactions as targets for therapeutic intervention
Figure The Biology of Cancer (© Garland Science 2007)

5. 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- SU11248
Bay

6. Inhibition of angiogenesis
inhibition of VEGF and VEGF signaling
mAb-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

10. Avastin (Bevacizumab) Genentech Inc. Effects on ATCC tumor cell lines
rhabdomyosarcoma
Avastin
(Bevacizumab)
Genentech Inc.
Effects on ATCC
tumor cell lines
glioblastoma
leiommyosarcoma

11. 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

14. Bevacizumab Colorectal cancer Phase III Combination therapy
Hurwitz et al. 2004
Mass et al. 2004
IFL:
Irinotecan
5-fluorouracil
leucovorin

15. Kabbinavar et al., 2005
5-fluorouracil
leucovorin

16. DC101 - VEGFR2 mAb

18. AZD21771 - Astra Zeneca - preclinical
ATP-competitive
VEGFR2 kinase inhibitor,
Mimics binding of
ATP adenine ring
AZD Astra Zeneca - preclinical

20. SU11248 - Sunitinib - Pfitzer
GIST (gastrointestinal stromal tumors
Kidney cancer
Approved 2006

21. Vascular tumor targeting

22. Gentherapien:
rAdenoviren
rRetroviren
Targeting of viruses to tumors, tumor endothelium
Targeting of liposomes to tumors, tumor endothelium
Oncolytic viruses
BM progenitor cells home to tumor vasculature