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Within the foreseeable future, patients will continue coming to hospital with cancerous tumours, which will be removed surgically. In some cases, the surgery will have cured the patient. In other cases, the cancer cells will have spread in the body of the patient and formed metastases already at the time of diagnosis. It is the metastases which may eventually kill the patient. Patients at risk of having metastases at the time of surgery should therefore be subjected to so-called adjuvant treatment, to prevent growth and further spread of the cancer cells. The problem is that the metastases are most often not detectable at the time of diagnosis. How does one distinguish between cured patients and patients at risk of recurrence of disease? The planning of post-surgery treatment is a current major challenge in oncology. And if metastases at later time points do eventually become clinically manifest, how are they best treated?
Ideally, the prediction of the need for adjuvant therapy should be based on molecular analysis of the primary tumour and/or blood samples. A variety of molecules has been found of interest as prognostic markers. Of particular interest are enzymes catalysing the degradation of proteins, the so-called proteases. Proteases, together with various co-operating factors, cause degradation of the normal tissue surrounding the cancer cells and enable them to invade into normal tissue and spread in the body. High tumour levels of components of one such protease system, the plasminogen activation system, are strong markers for a poor prognosis and can be used to select patients for adjuvant therapy. In fact, the American Society for Clinical Oncology now recommends measurements of this protease system for evaluating prognosis and treatment possibilities for breast cancer patients. Moreover, much evidence supports the idea that inhibition of proteases can be used to inhibit growth and spread of cancer cells. An important aspect is to develop methods for characterising metastases with respect to their content of specific protein-degrading proteases. The availability of specific inhibitors will then allow intervention with exactly the proteases present in the metastases of individual patients and then make an important contribution to an optimal individualised treatment.
With the purpose of promoting such research, the Danish National Research Foundation and the National Natural Science Foundation of China have decided to support a virtual research centre formed by the research groups of Mingdong Huang, Fujian Institute of Research into the Structure of Matter, Chinese Academy of Sciences, Fuzhou; Dongxu Liu, School of Life Sciences, Hubei University, Wuhan; Michael Ploug, Niels Behrendt, and Andreas Kjær, Copenhagen University Hospital; Peter Andreasen, Jørgen Kjems, and Niels Christian Nielsen, members of the iNANO centre in Aarhus. The work in “Danish-Chinese Centre for Proteases and Cancer” focuses on finding new types of protease inhibitors based on three-dimensional structure of the protease-inhibitor complexes, and testing the inhibitors in animal tumour models. The combination of basic molecular characterisation of these protease systems with modern methods of molecular imaging may eventually result in improved treatment possibilities for cancer patients.