Tracking down metastases
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Most cancer patients do not die of the original tumour, but rather of the metastases. Hence, the worried question asked when cancer is diagnosed is: Will the tumour spread? As far as colon cancer is concerned, at least, this uncertainty may soon be a matter of the past. Cancer researchers at the Max Delbrueck Center for Molecular Medicine (MDC) Berlin-Buch and the Charité Universitätsmedizin Berlin have identified several genes which could, in the future, make it possible to predict the course of the disease and lead to a more targeted therapy. Some 73,000 people contract colon cancer every year in Germany.
Chemotherapy and radiation therapy manage to cure around half the patients. However, some 20 per cent of those affected already have metastases when they are diagnosed and in around a third of the cases metastases later develop despite the success of the first therapy. More than 25,000 die of colon cancer every year in Germany. It is the second most common cause of death among cancers, only second to lung cancer. This is why the aim is to recognise patients who have a high risk of developing life-threatening metastases in the liver, lung or lymph nodes at an early stage so that they can be more intensively treated and cared for. The cancer researchers at the MDC and Charité have moved a step closer to this goal. They discovered a gene that for the first time makes it possible to predict with a high probability the formation of metastases in colon cancer at an early stage. Then they soon found more than a hundred genes suspected of advancing the dangerous spread of colon cancer.
The first metastasis gene MACC1, discovered by Prof. Dr. Ulrike Stein, Prof. Dr. Peter M. Schlag and Prof. Dr. Walter Birchmeier, not only promotes cancer growth, but also the formation of metastases. “When MACC1 activates a certain signalling pathway, cancer cells can grow more quickly, can break away from their cell groups and can settle as metastases in organs located far away from the original tumour,” explains Stein.
The researchers were able to show that patients suffering from colon cancer have a longer life expectancy if the activity level of the MACC1 is low. On the other hand, colon cancer patients with high MACC 1 levels have a much greater risk of metastasis and so a less favourable survival prognosis. The researchers tracked down the gene by comparing healthy tissue with the tissue samples of 103 colon cancer patients.
Of these patients, 60 were free of metastases at the time of their operation. 37 were still free of metastases five years after the operation and therapy. When they were first diagnosed, they had low MACC 1 levels in the colon tumours. 23 patients, however, had developed metastases after five years. They had shown high MACC 1 levels in the tumour tissue. Whether the newly discovered metastasis gene also allows a more exact prediction of the course of other cancers is still an open question. To see what genetic changes favour the formation of metastases, Dr. Johannes Fritzmann and his colleagues from the MDC and Charité examined 150 tissue samples from colon cancer patients with and without metastases.
They identified 115 genes that have mutated both in the primary tumour as well as in the metastases that it formed and so discovered a genetic signature that differentiates between metastatic and non-metastatic tumours. The researchers examined one of the 115 genes in closer detail and discovered that one gene, called BAMBI, is more active in metastatic tumours and metastases than in tumours that do not form any metastases. BAMBI connects two important signalling pathways and so promotes the formation of metastases. The cancer researchers hope that their results will contribute to indicating at an early stage whether a tumour will spread or not. Then the physicians could decide whether a patient requires a more intensive therapy or whether the patient can be spared from this.
