Mathematical models of the VEGF receptor and its role in cancer therapy.
We present an analysis of a stochastic model of the vascular endothelial growth factor (VEGF) receptor. This analysis addresses the contribution of ligand-binding-induced oligomerization, activation of src-homology 2 domain-carrying kinases and receptor internalization in the overall behaviour of the VEGF/VEGF receptor (VEGFR) system. The analysis is based upon a generalization of a Wentzel-Kramers-Brillouin (WKB) approximation of the solution of the corresponding master equation. We predict that tumour-mediated overexpression of VEGFRs in the endothelial cells (ECs) of tumour-engulfed vessels leads to an increased sensitivity of the ECs to low concentrations of VEGF, thus endowing the tumour with increased resistance to anti-angiogenic treatment.
Alarcón
Tomás
T
Bioinformatics Unit, Department of Computer Science, University College London, Gower Street, London WC1E 6BT, UK. tomasalarc@googlemail.com
Page
Karen M
KM
D000818:Animals; D019281:Dimerization; D004705:Endocytosis / Q000502:physiology*; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply / Q000628:therapy*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D018909:src Homology Domains / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor