Pathological blood vessel formation (angiogenesis), or the inability of endothelial cells to perform their physiological function (endothelial dysfunction), are defining features of disease. The endothelium actively controls vessel integrity, vascular growth and remodelling, tissue growth and metabolism, immune responses, cell adhesion, angiogenesis, haemostasis and vascular permeability. It is, therefore, a vital and largely unexploited target for novel therapies.
Prof Tracy Robson’s team have identified and characterised a novel anti-angiogenic protein, FK506 binding protein like – FKBPL, significantly advancing our understanding of the anti-angiogenic process, in particular, how tumours recruit blood vessels to support their growth. This led to a collaborative study with Almac Discovery to develop therapeutic peptides based on FKBPL’s active domain to explore their potential in cancer by targeting the ability of tumours to recruit blood vessels to grow, invade and metastasise beyond the site of the primary tumour. The team are also testing the ability of these peptides to sensitise tumours to current therapies and to target cancer stem cells that lead to the onset of resistance and/or recurrent disease. Importantly, these studies led to a ‘first in man’ phase I clinical in cancer patients where the clinical candidate drug, ALM201, was very well tolerated over a wide range of doses. Prof Robson’s team (Dr Stephanie Annett and Dr Gillian Moore) will discuss this data together with new data suggesting a strong role for FKBPL in vascular endothelial dysfunction and possible implications therefore in other diseases associated with vascular disease.