Whereas the pivotal role of VEGF and VEGFR-2 has been amply documented, one particular line of evidence, based on pre-clinical animal models, suggests that targeting VEGF-VEGFR signalling and focusing on endothelial cells is beneficial at the start of treatment, but with continued drug treatment and under the pressure of VEGF signalling blockade resulting in increased hypoxia and malnutrition on the tumour cells, other signalling molecules and their cognate receptors provide alternate mechanisms to drive disease progression. Here, VEGFA is linked to neoplasm.