PMID: 11908675Mar 23, 2002Paper

Vascular endothelial growth factor and vascular targeting of solid tumors

Anticancer Research
Rolf A Brekken, P E Thorpe

Abstract

Vascular targeting agents, which selectively destroy tumor blood vessels, are attractive agents for the treatment of solid tumors. They differ from anti-angiogenic agents in that they target the mature, blood-conducting vessels of the tumors. They are better suited for larger tumors where angiogenesis can occur less frequently. For application in man, target molecules are needed that are selectively expressed on the vascular endothelium of tumors. Such markers include the complexes that are formed when vascular endothelial growth factor (VEGF) binds to its receptors (VEGFR). VEGF production by tumor cells is induced by oncogenic gene mutations and by the hypoxic conditions within the tumor mass. The receptors, VEGFR1 (FLT-1) and VEGFR2 (KDR/Flk-1), are upregulated on vascular endothelial cells in tumors by hypoxia and by the increased local concentration of VEGF. Consequently, there is a high concentration of occupied receptors on tumor vascular endothelium. Here, we review the concept of vascular targeting and the development of monoclonal antibodies that bind to VEGF: VEGFR complexes and their use as tumor vascular targeting agents. A promising monoclonal antibody is 2C3, which blocks VEGF from binding to VEGFR2 but not VEGFR...Continue Reading

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