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Research into the structure of blood vessels in tumours, published in Nature, has opened the way to improve targeted cancer therapy.

The blood vessels that grow through tumours are not like other blood vessels. Their cells are disorganised and their walls are fragile and leaky. These abnormal structures make it more difficult for the patient's immune system to attack the tumour and for immune-based therapies to target the tumour cells. An enormous amount of work is being done around the world to understand these processes and how they are controlled so that new treatments can be developed.

During their investigations into this area, Prof. Ruth Ganss and her colleagues at the Western Australian Institute for Medical Research and Centre for Medical Research at UWA, have made a fascinating and unexpected discovery. RGS5 is an intracellular signalling protein that is normally present in some specialised cell types in the body and is seen in increased amounts in tumour blood vessels. By using confocal microscopy at CMCA, Ruth's group has looked at the structure of tumour blood vessels in mouse mutants lacking the Rgs5 gene (and therefore having no RGS5 protein). Their exciting finding is that the removal of the gene leads to tumour blood vessels that look normal rather than disorganised. The normal blood vessels actually lead to a small increase in oxygen getting to the tumour, which is initially to the tumour's benefit; however, immune cells that normally have problems getting through the abnormal blood vessel walls can now pass through easily, which opens the way for treatments with activated immune cells.

Before that can happen, RGS5 needs to be studied in much more detail to gain an understanding of the signalling pathways it controls. It would then be necessary to develop a drug to block RGS5 functioning in the tumour blood vessels. Such a drug could be used in combination with activated immune cell therapies and would hold out real hope for a highly effective treatment.

J. Hamzah, M. Jugold, F. Kiessling, P.J. Rigby, M Manzur, H.H. Marti, T. Rabie, S. Kaden, H.J. Gröne, G.J. Hämmerling, B. Arnold and R. Ganss, Vascular normalization in Rgs5-deficient tumours promotes immune destruction, Nature , 453: 410-454, 2008.

Published in the AMMRF Annual Profile 2009