Objective of this project is to optimise Notch inhibitors for the treatment of cancer cells and tumour associated angiogenesis. We hypothesise that there is a bi-directional cross talk between cancer cells and endothelial cells in their microenvironment, which acts to promote cancer growth and invasion, as well as malignant neo-angiogenesis. We further hypothesise that Notch signalling is one of the key mediators of this cross talk, and that depending on the pattern of expression of Notch receptors and ligands between cancer cells and endothelial cells, the nature of this cross talk, and therefore cancer aggressiveness and response to distinct Notch inhibitors will be different. This would imply that in order to choose the optimal Notch inhibitor for each patient in the clinic, we need to know the nature of this intricate crosstalk.