Combination therapy in aggressive childhood brain tumor
Diffuse midline glioma (DMG) is a group of fast-growing brain tumors that mainly occur in children. It is an incurable form of childhood cancer – on average, children die nine to eleven months after diagnosis. A new experimental drug, ONC201 shows promise: in early trials in the United States, it has doubled survival in children with DMG. In the Máxima, some children are eligible for this new treatment as part of the international clinical trial network PNOC.
The results from the first trials are encouraging, but after a while ONC201 stops working. Dr. Esther Hulleman, research group leader at the Máxima, will use the new funding to investigate why DMG tumors become insensitive to the drug. She will look at the effect of ONC201 on the immune system in mice. Which parts of the immune system play a role in the reduced response? She will also examine which genes in the tumor have an effect on how well the drug works.
By first unraveling the effect of ONC201, Hulleman can specifically search for another drug that, in combination with ONC201, can prolong the effect and thus improve the treatment of children with DMG. The members of the international PNOC network can feed into the study. If the new project points to a better combination treatment, it could be given to children with DMG within the clinical trial.
Targets for therapy in Hodgkin lymphoma
Hodgkin lymphoma is a form of blood cancer that occurs mainly in young adults. Around 40 children in the Netherlands are diagnosed with the disease each year. Chemotherapy treatment works well – almost all children with Hodgkin lymphoma are cured. But they can suffer from serious side effects during treatment or later in life. They can for example develop lung or heart disease, have reduced fertility and a higher risk of a second cancer.
In the new research project, pediatric oncologist dr. Friederike Meyer-Wentrup will look for clues for a new, targeted treatment for Hodgkin lymphoma. Targeted treatments specifically attack the tumor cells and leave healthy cells alone. As a result, they cause fewer, or less serious, side effects and late effects.
In Hodgkin lymphoma, the tumor cells depend on normal immune cells to survive. They 'talk' to each other by exchanging signals. Meyer-Wentrup will grow tumor and benign cells from children with Hodgkin lymphoma in the lab. She will investigate how to interrupt the signals between the two types of cells so that the tumor cells die. This could lead to new targets for the development of better treatment for children and adults with this form of lymphoma.
KWF has awarded a total of €1.2 million for these two research projects.