The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis and early clinical development of VEGF-receptor kinase inhibitors.

H. M. Verheul, H. M. Pinedo

Research output: Contribution to journalArticle

Abstract

Angiogenesis, or the formation of new blood vessels from preexisting vasculature, plays a major role in tumor growth and metastasis formation. Therefore, inhibiting tumor angiogenesis may be a promising therapeutic strategy. Paracrine stimuli from tumor cells are the main promoters of angiogenesis. They activate endothelial cells to proliferate and migrate, subsequently resulting in new tube formation and blood flow. This complex process involves numerous biological activities. Vascular endothelial growth factor (VEGF) is a potent and specific angiogenic factor. Originally identified for its ability to induce vascular permeability and stimulate endothelial cell growth, VEGF is now known to be a key requirement for tumor growth. Currently, three high-affinity tyrosine kinase receptors for VEGF have been identified, of which VEGF receptor (VEGFR)-Flk-1/KDR (VEGFR-2) is exclusively expressed in vascular endothelial cells. Because the VEGFR-2 system is a dominant signal-transduction pathway in regulating tumor angiogenesis, specific inhibitors of this pathway inhibit metastases, microvessel formation, and tumor-cell proliferation. Induction of apoptosis in tumor cells and endothelial cells has also been observed. The clinical importance of VEGF for tumor growth is supported by the fact that most tumors produce VEGF and that the inhibition of VEGF-induced angiogenesis significantly inhibits tumor growth in vivo. In this review, we discuss the biologic role of VEGF and the therapeutic options for inhibiting VEGF in cancer patients.

Original languageEnglish (US)
JournalClinical Breast Cancer
Volume1 Suppl 1
StatePublished - Sep 2000
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor
Vascular Endothelial Growth Factor A
Phosphotransferases
Neoplasms
Endothelial Cells
Growth
Neoplasm Metastasis
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
Angiogenesis Inhibitors
Angiogenesis Inducing Agents
Capillary Permeability
Receptor Protein-Tyrosine Kinases
Microvessels
Blood Vessels
Signal Transduction
Cell Proliferation
Apoptosis

ASJC Scopus subject areas

  • Cancer Research

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The role of vascular endothelial growth factor (VEGF) in tumor angiogenesis and early clinical development of VEGF-receptor kinase inhibitors. / Verheul, H. M.; Pinedo, H. M.

In: Clinical Breast Cancer, Vol. 1 Suppl 1, 09.2000.

Research output: Contribution to journalArticle

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