Elisabetta Dejana – New strategies to inhibit tumour angiogenesis

Microscope image of blood vessels Our research is focused at understanding the mechanisms that regulate the formation of the vascular system in tumours in order to induce their regression.

One of the innovative aspects of anti-cancer therapies concerns the possibility of inhibiting tumour growth by blocking blood supply. The simple idea is that, if starved, the tumour 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 tumour 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 tumour vessels may be important to improve perfusion of the tumour microenvironment and, ultimately, improve cancer treatment. Furthermore, the normalized vasculature may be more resistant to tumour cell infiltration and metastatic dissemination.

Our research aims to clarify the mechanisms behind the formation of the tumour vasculature. Our approach includes studies in vivo, using tumour models and genetically modified organisms, and in vitro, using cultured endothelial cells of different origin.