Prof Elisabetta Dejana
Professor of General Pathology at the Department of Biosciences, University of Milan

One of the innovative aspects of anti-cancer therapies concerns the possibility of inhibiting tumor growth by blocking blood supply. The simple idea is that, if starved, the tumor will not grow but, on the contrary, will shrink and become more susceptible to chemotherapy and radiotherapy. Cancer cells induce the formation of their own vascular system by recruiting new vessels from the host. However, the resulting vasculature is structurally and functionally abnormal. The vessels are leaky, tortuous, dilated and have lost hierarchy. The endothelial cells lining these vessels have aberrant morphology and are frequently retracted exposing the underlying matrix and tumor cells to the blood stream. These structural abnormalities cause edema and hemorrhages contributing to interstitial hypertension, hypoxia, and acidosis. Impaired blood supply and interstitial hypertension create areas of necrosis and interfere with the homogeneous delivery of therapeutics. These observations suggest that normalization of tumor vessels may be important to improve perfusion of the tumor microenvironment and, ultimately, improve cancer treatment. Furthermore, the normalized vasculature may be more resistant to tumor cell infiltration and metastatic dissemination. In general our research is focused at understanding the mechanisms that regulate the formation of the vascular system in tumors in order to induce their regression.
Our approach include studies in vivo using tumor models and genetically modified organisms and in vitro using cultured endothelial cells of different origin.