ScienceVEGF

Endothelial cells and VEGF are genetically stable targets

The regulation and stability of important processes in tumourigenesis is illustrated in this image.^1–6

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As observed in preclinical models, considerable variation may exist in the genetic stability of important antitumour targets. For example, kinase receptors on tumour cells may be susceptible to genetic mutation.⁷ Moreover, the process of tumour proliferation is mediated largely through autocrine signalling, in which a tumour cell secretes an agent (such as EGF) that acts upon the same cell type.⁸ Genetic mutations within these cells may destabilise the pathway, potentially limiting the ability to continually target this process.^1,2

 

In contrast, based on preclinical observations, it has been proposed that both the endothelial cell and VEGF are genetically stable.⁹ VEGF is part of a predominantly indirect paracrine signalling pathway – the angiogenic pathway – in which the secretion of growth factors from tumour cells affects activity on nearby, yet distinct, endothelial cells.^3–5,9 The stability of VEGF and the endothelial cells in non-cancerous cells makes continued targeting of this pathway an important antitumour strategy.