Angiogenesis is the mechanism of blood vessel formation from pre-existing ones and is vital for nutrient and oxygen delivery to all cells in the organism. However, dysregulation of angiogenesis is detrimental for the organism. Excessive or abnormal angiogenesis is a hallmark of cancer and various retinopathies and favours tumour growth and metastasis, and vision loss, respectively. Excessive or abnormal angiogenesis is fuelled by hypoxia-driven expression of high levels of vascular endothelial growth factor A (VEGFA), the main pro-angiogenic molecule that stimulates the formation of new blood vessels. Although VEGFA-centric anti-angiogenic therapies do exist, their efficacy is limited by their specificity and numerous side effects, hampering greatly their potential clinical benefits. Therefore, there is an urgent need for improved anti-VEGFA therapeutic strategies.
The VECARE project aimed to identify a novel class of anti-VEGFA drugs to curb cancer and retinopathies. As part of the ERC starting project AXIAL.EC our group has generated a novel cellular system suitable to track vascular endothelial growth factor (VEGFA) amenable to high-throughput screening. We performed a high-throughput screening to identify molecules promoting VEGFA retention in vivo. We successfully identified several lead compounds that uniquely promote VEGFA retention, which were selected for further validation in vitro and in vivo. We validated lead compounds effects on endogenous VEGFA in several cancer cell lines in vitro. From 6 lead compounds that were tested, we identified 2 lead compounds that promote efficient retention of VEGFA in human cancer cell lines and not in mouse cancer cell lines. We are now testing the efficacy of these lead compounds in preclinical mouse models of cancer. Our project will deliver a novel class of anti-cancer and/or anti-retinopathies drugs. It will surely contribute to improving patient survival and well-being, and reducing the economic burden associated with these diseases.
