Research teams led by the University of Pennsylvania have now discovered in a study on a mouse model that inhibitors that could be taken as drugs in the future could reduce or prevent the metastatic spread of melanoma cells in the skin. This would increase the survival time of people with this aggressive form of cancer. The spread of melanomas in mice was illustrated with the help of an enzyme, p38alpha kinase. It was shown that inhibitors of the p38 enzyme, p38 for short, which is involved in the activation of cancer cells, intervene in the process and reduce it. The scientists incorporated aspects of cancer biology into their research. tumours, they secrete different compounds including proteins and hence also enzymes, lipids, vesicles, other genetic material and signalling molecules which then circulate in the body. Scientists refer to such factors as tumor-derived factors (TDF), which help to prepare the growth of metastases. p38 also reacts in a similar way and is activated. However, certain tissue types are more susceptible to tumor cells due to certain factors. In the mouse model, the researchers found confirmation that mice form so-called pre-metastatic niches when they are provided with the aggressive form of TDF. In order to then stop or prevent the metastasis process and reach the pre-metastatic niche, the researchers blocked the kinase activity and hence the activated signalling pathway of the enzyme with two different inhibitors after infecting the lungs of the mice with TDF. If one now compares animal studies with a clinical context, it became clear that a significantly lower p38 activity was found in humans without signs of metastasis after the development of skin cancer. This showed the research group that forms of therapy with two different inhibitors, which keep the activity of the enzyme in check, in combination with surgery to remove the primary tumour in skin melanomas or in combination with chemotherapy can lead to success if both treatments can prevent the spread and metastasis of cancer, as illustrated in animal experiments. The first results of the studies have already been published in the English-language journal „Nature Cancer“.
