Five studies start thanks to KiKa

Each of the studies funded by KiKa contributes to achieving the mission of research hospital the Princess Máxima Center: To cure every child with cancer, with optimal quality of life.

Detecting residual disease via blood and bone marrow in children with soft tissue cancer

Treatment of tumors of the soft tissue, in the muscles (rhabdomyosarcoma) or other supporting tissue (non-rhabdomyosarcoma) is intensive. Despite chemotherapy, radiation and surgery, the disease recurs in one in three children. To further improve treatment, an international study will soon begin. Researchers will examine a large group of children to see if they can detect so-called residual disease in the blood and bone marrow. They will do this using previously developed methods to detect the DNA and RNA that tumor cells release into the bloodstream. Postdoctoral researcher on this project and pediatric oncologist in training Dr. Nathalie Lak: 'If we conclude that we can detect residual disease in the blood, we may be able to better adjust treatment for each child from the time of diagnosis: make it more intensive or, on the contrary, less intensive.' In this project, Lak collaborates with pediatric oncologists and researchers Prof. Dr. Lieve Tytgat, Prof. Dr. Hans Merks and Prof. Dr. Max van Noesel.

Origin of childhood cancer and the possible role of 'adult' mutations

Hereditary predisposition plays a role in about 10% of children with cancer. Several studies have shown that children with cancer more often than expected carry a harmful congenital change in their genes that we know mainly from predisposition to cancer in adulthood. Prof. Dr. Roland Kuiper, research group leader: 'In this project, I want to learn more about the role these mutations played in the development of childhood tumors. To do this, we will collect DNA from tumors and blood from about 150 children with cancer who have a DNA change in such an 'adult' cancer gene. In the DNA of the tumors, we are looking for patterns that indicate that the mutation played a role in the development of the tumor. In addition, we are looking for other DNA changes that may have caused cancer together with the 'predisposition gene.' Kuiper hopes the research will lead to a better understanding about the origins of childhood cancer. He also hopes to establish policies around testing and that children will have access to treatments developed for tumors caused by these 'adult' cancer genes.

 

Ewing sarcoma is a rare bone tumor in children that is treated with radiation, surgery or chemotherapy. After treatment, there is a chance that the tumor will still come back in the same place or in another part of the body. Few effective drugs are available for these children. That is why Dr. Meta Diekstra is looking into this together with her colleague Dr. Shunya Ohmura from Germany. 'New research shows that the drug disulfiram, when combined with the chemical element copper, can have an anti-tumor effect in different types of tumors in adults and thus possibly also in children. Our goal is to develop a new child-friendly drug in which we wrap the combination of disulfiram and copper in a package that is only delivered once it arrives at the tumor. That way it can work very precisely on the tumor.' The efficacy of the combination will first be tested in mice. If this leads to good results, a clinical study will start for children with Ewing sarcoma. Because we are reusing an existing drug, development costs less time and money.

 

Some children who develop leukemia again may be treated with CAR T-cell therapy. In this form of immunotherapy, the child's immune cells are modified so that they recognize and target cancer cells. However, after this treatment, the leukemia still returns in 40 to 50% of children. So the big question for Dr. Stefan Nierkens, research group leader and medical immunologist, and his team is: Why do CAR T-cells work well in one child, but not in another? Nierkens: 'Previously, we saw that the immune system responds differently when children have high or low exposure to fludarabine. This drug is used to reduce normal T-cells in number so that there is more room for CAR T-cells. We want to understand why the immune system responds differently and investigate exactly how much fludarabine needs to be given for the CAR T-cells to work optimally. We also want to make the CAR T-cells work longer, so that leukemia returns in fewer children.' What Nierkens and his colleagues learn from this research could potentially be used in the development of CAR T-cell therapies for adults and children with other types of cancer. In addition to Nierkens, the research team includes pediatric oncologist Dr. Friso Calkoen and Dr. Rick Admiraal, pediatric oncologist in training and clinical pharmacologist.

 

Recently, drugs that trigger the child's immune system to clear leukemia cells have been used in the treatment of children with acute lymphoblastic leukemia (ALL). However, these immunotherapies do not always work optimally. One reason is that the leukemia cells modify the bone marrow, the place in the bones where leukemia develops. As a result, the healthy immune cells do not respond well to the drug and thus fail to act. Prof. Dr. Monique den Boer, research group leader: 'We have clues how leukemia manipulates the bone marrow very locally. In this Kika project, we are investigating how we can remove the inhibitory effect.' In this way, den Boer, together with postdoctoral researcher Dr. Cesca van de Ven, hopes that insensitivity to immunotherapy can be prevented and possibly used earlier in the treatment process in the future.

KiKa is awarding the researchers a total of €2.8 million for these five projects. KiKa is an important partner of the Princess Máxima Center. KiKa supports pediatric cancer research at the Máxima through core funding and has already made numerous research projects possible.