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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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angiogenesis
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.

Angiogenesis
vegf family and receptors
VEGF 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 Receptors
anti vegfr 2 antibody reduces tumor interstitial pressure
Anti–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 k i
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
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 in prostate cancer xenografts
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 Xenografts
ptk787 zk 222584 reduces liver metastasis perfusion
PTK787/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
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.