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Sprouting angiogenesis involves multiple linked and sequential steps that include endothelial cell proliferation, migration, invasion, survival, and capillary tube formation; mediated by multiple angiogenic factors, the most important of which is VEGF.
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Sprouting angiogenesis involves multiple linked and sequential steps that include endothelial cell proliferation, migration, invasion, survival, and capillary tube formation; mediated by multiple angiogenic factors, the most important of which is VEGF.
Ellis. Horizons in Cancer Therapeutics. 2004;5(2):4-10.
AngiogenesisVEGF family members bind to specific VEGF membrane-bound tyrosine kinase receptors, eliciting the functions described in this slide.
Ellis. Horizons in Cancer Therapeutics. 2004;5(2):4-10.
VEGF Family and ReceptorsAnti–VEGFR-2 Antibody Reduces Tumor Interstitial Pressure
Treatment with anti–VEGFR-2 antibody led to a rapid reduction in murine lung and glioma tumor interstitial pressures. From Tong et al. Cancer Res. 2004;64:3731-3736, with permission.Ellis. Horizons in Cancer Therapeutics. 2004;5(2):4-10.
PTK787/ZK 222584 Reduces Liver Metastasis Ki
PTK787/ZK 222584 reduced perfusion parameters (Ki) in nonprogressing patients with colorectal cancer liver metastasis. From Morgan et al. J Clin Oncol. 2003;21:3955-3964,with permission.
Ellis. Horizons in Cancer Therapeutics. 2004;5(2):4-10.
Modulating VEGF/VEGFR Signaling
Vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) signaling modulation approaches include targeting VEGF/VEGFR with antibodies, reducing VEGF expression with fusion proteins, using ribozymes to decrease receptor expression and activation, and reducing receptor activation and downstream signaling.
TKI = tyrosine kinase inhibitors.
Steward. Horizons in Cancer Therapeutics. 2004;5(2):11-21.
PTK787/ZK 222584 (PTK/ZK) significantly inhibited human DU-145 prostate cancer xenografts in nude mice. Tumor growth resumed on cessation of treatment, demonstrating the cytostatic rather than cytotoxic effects of PTK/ZK. From Bold et al. Prous Sci Drugs Future. 2002;27:43-55, with permission.
Steward. Horizons in Cancer Therapeutics. 2004;5(2):11-21.
PTK787/ZK 222584 in Prostate Cancer XenograftsPTK787/ZK 222584 Reduces Liver Metastasis Perfusion
Baseline (top) and day 2 (bottom; ~30h postdose) images show reduction in perfusion and permeability of liver metastasis (arrow) after bolus PTK787/ZK 222584. From Morgan et al.J Clin Oncol. 2003;21:3955–3964, with permission.
Steward. Horizons in Cancer Therapeutics. 2004;5(2):11-21.
PTK787/ZK 222584 Reduces Liver Metastasis Volume
MRI images from a colorectal cancer patient show a reduction in liver metastasis(highlighted by shaded areas in lower panels) after PTK787/ZK 222584.
Steward. Horizons in Cancer Therapeutics. 2004;5(2):11-21.
