Tumours often have diverse types of cells and characteristics, which makes them difficult to treat. Radiotherapy and chemotherapy do kill cancer cells, but they also damage healthy tissue. In addition, metastases make a successful treatment even more complicated. There is thus clearly a need for precisely targeted methods of treatment. This is exactly what the radiotherapy department and the research team led by Prof. Marc Vooijs have been doing research on for some considerable time and for which they have now been awarded a grant.

Cancer stem cells
The research is focused on two substances that have the ability to shut down the development process of cancer stem cells. This type of stem cell maintains the diversity within a tumour through the continuous division and self-renewal of cancer cells. This also makes the tumour resistant to therapy, which has the consequence of increasing the likelihood of metastases. A key process in the development and division of cancer stem cells is called NOTCH. If this process is shut down, the cells stop dividing and the tumour becomes more susceptible to therapy. One of the two promising substances (called PSEN2 inhibitor) is intended for exactly that purpose and it is so specific to the tumour that healthy cells (in which NOTCH is also active) are spared.

Low-oxygen parts of the tumour
The other substance that the researchers are interested in only becomes active in the low-oxygen parts of a tumour. These areas are a sign that the tumour can behave aggressively, is resistant to both chemotherapy and immunotherapy, and therefore has an unfavourable prognosis. The substance (called HyGSI dual-specificity inhibitor) also shuts down the development process of the cancer stem cells, but only becomes active in low-oxygen areas, which are normally not present in healthy tissue.

Business case
The researchers are now going to demonstrate further the effectiveness of both substances in mice, before they can take the next step towards being able to use the therapy on patients. "In addition, we are also working on a business case," says lead researcher Vooijs. "In this way, we can act quickly if our research results are positive. Being in a position to actually market a medicine that is suitable for patients is still years away, but our research is also increasing our understanding of the mechanism of tumours. This knowledge is very valuable."

The research project is entitled INGSIGHT (Inhibition of notch/ g-secretase in hypoxic tumours). Prof. Marc Vooijs is one of five Dutch scientists to be awarded an ERC grant in this round. For Vooijs, this is the fourth such grant in his career.