Mathematical models of the VEGF receptor and its role in cancer therapy |
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Authors: | Toms Alarcn and Karen M Page |
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Affiliation: | Bioinformatics Unit, Department of Computer Science, University College London, Gower Street, London WC1E 6BT, UK. tomasalarc@googlemail.com |
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Abstract: | 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. |
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Keywords: | angiogenesis vascular endothelial growth factor receptor tyrosine kinase oligomerization endocytosis master equation |
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