Control of tumour vascular permeability.
Several model tumour systems are now known to display increased vascular permeability compared with normal tissues, permitting their selective targeting using macromolecular drugs. Preliminary clinical observations suggest that this pathology may be reflected in at least some types of human cancer, and this may have important implications in facilitating macromolecular drug treatments, including antibody targeting and delivery of DNA for gene therapy. The enhanced permeability of tumour vasculature is thought to be regulated by tumour-secreted growth factors, with vascular permeability facor (VPF), also known as vascular endothelial growth factor (VEGF), emerging as a particularly likely candidate. VPF/VEGF is known to be an important regulator of tumour-angiogenesis in vivo, and it exerts its endothelium-specific effects via its receptors KDR/Flk-1 and Flt-1 on the endothelial cell membrane. Although the precise mechanism of VEGF's permeabilising action is not yet understood, it is likely to contribute to the enhanced permeability and retention (EPR) effect in tumours which is thought to underlie the anticancer activity of macromolecular drugs.
Baban
DF
CRC Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TT, UK
Seymour
LW