The Cheresh laboratory studies tumor angiogenesis and tumor cell invasion and metastasis. They have developed a number of inhibitors of tumor angiogenesis that are now being tested clinically in cancer patients. Two of these agents, Vitaxin and Celingitide, show promise for late stage cancer patients and appear safe with little or no side effects.
Their basic research efforts primarily deal with the study of molecular mechanisms that regulate tumor cell and endothelial cell survival, migration and invasion. They focus on signaling pathways initiated by extracellular matrix proteins, integrins and growth factor receptors that influence the biology of tumor cells and angiogenic endothelial cells.
Cheresh and his colleagues have a particular interest in alpha V integrins and their ligands and how integrins regulate the epithelial to mesenchymal transition. They previously reported that integrins avb3 and avb5 mediate distinct mechanisms of angiogenesis regulated by the growth factors basic fibroblast growth factor and vascular endothelial cell growth factor, respectively. These pathways are characterized by distinct signaling pathways and differential activation of Raf kinase in endothelial cells.
More recently they have begun to develop small molecule Raf kinase pathway inhibitors that promote endothelial cell apoptosis and serve to disrupt angiogenesis and tumor growth.