Design, synthesis and evaluation of new integrin-targeting drugs

The integrins are a family of transmembrane receptors which mediate cell-cell and cell-ECM adhesion, and signalling across the cell membrane involved in pathways controlling cell migration, proliferation, differentiation, cell survival and apoptosis. In cancers, their vital role in the cross-talk between the cell and extracellular matrix enhances the growth, migration, invasion and metastasis of cancer cells. The RGD-binding subfamily of integrins are of particular interest as anticancer targets, since there is strong evidence that their expression in cancers is correlated with tumour progression, treatment resistance, and a cancer stem cell phenotype. This project involves the synthesis and characterisation of new integrin targeting small molecules for the treatment of advanced cancers, focussing on the tools and models required to target integrin alphavbeta8.