International collaboration is essential in childhood cancer research: analyzing data from larger numbers of children and sharing knowledge helps improve and speed up scientific progress. Right from its opening five years ago, the Princess Máxima Center has held a strong international position in the field of childhood oncology. To build on this, the Princess Máxima Center, the Hopp Children's Cancer Center Heidelberg (KiTZ), the German Cancer Research Center (DKFZ) and the Heidelberg University Hospital (UKHD) joined forces in a twinning program in 2021. Twelve collaborations are already underway, with nine new joint projects starting this year.
Brain tumors
Children with a brain tumor tend to have a poor outcome from their disease. Three of the joint projects will focus on these forms of childhood cancer. Dr. Esther Hulleman at the Máxima Center and dr. Marcel Kool at the Máxima and the Hopp-KiTZ will look at a possible new targeted treatment for so-called ependymomas, a tumor in the hindbrain. A particular type of ependymomas is characterized by high levels of the molecule GD2. In this project, the team aim to find out if GD2 could be a good target for immunotherapy in ependymoma.
As childhood cancer is rare, international collaborations are key to make sure enough children take part in clinical trials to test the benefit of new treatments. Dr. Jasper van der Lugt at the Máxima Center together with dr. Cornelis van Tilburg at KiTZ aim to pave the way for European hospitals to take part in the US-based PNOC and CONNECT clinical trial networks. In this way they aim to speed up clinical research into childhood brain tumors, as well as giving more children access to the newest, most promising drugs in a trial setting.
Research into childhood brain tumors makes use of tissue samples that are taken during surgery. A team led by dr. Stefan Nierkens at the Máxima Center and dr. Kendra Maass at KiTZ will look at samples of the fluid surrounding the brain and spinal cord (cerebrospinal fluid, or CSF) as a less invasive way to study these forms of childhood cancer. They aim to find molecular clues that could help point to immunotherapy strategies. CSF is sampled with a lumbar puncture, done under sedation. As CSF can be sampled more often, they also hope to better monitor the course of the disease and how the tumor responds to treatment.
Targeted treatments
The idea of precision medicine is to specifically target tumor cells, leaving healthy cells alone. That is the focus of a number of projects in the Twinning Program between the Princess Máxima Center and KiTZ. Children with liver cancer are treated with intensive chemotherapy and surgery, often even involving a liver transplant. New, more targeted treatments are needed, but research is challenging as liver tumors in children are very rare. A team led by dr. Weng Chuan Peng and dr. József Zsiros at the Máxima Center, together with dr. Ina Oehme and Marta Emperador at KiTZ will look at ways to model childhood liver tumors in the lab. Eventually the team aims to identify existing targeted drugs that could hold promise for children with liver tumors.
Early findings suggest that an existing class of targeted drugs, called MEK-inhibitors, could work well in children with a high-risk form of Wilms’ tumor, the most common form of kidney cancer in children. A team led by dr. Jarno Drost at the Máxima Center and dr. Robert Autry at KiTZ will study the effect of MEK-blockers in mini-Wilms’ tumors in the lab. If this class of drugs looks promising in these organoids, it could pave the way for further development of MEK-blockers as a treatment strategy for children with a Wilms’ tumor whose cancer is more aggressive due to a fault in the SIX1 gene.
The collaborative projects are funded by the Princess Máxima Center Foundation and the foundations of the German centers. Four more joint projects have been announced:
A team led by dr. Sebastiaan van Heesch and prof. dr. Hans Merks at the Princess Máxima Center, together with prof. dr. Thomas Grünewald at KiTZ will look at evolutionarily young small proteins in Ewing sarcoma, with the aim of finding new targets for therapy.
Prof. dr. Olaf Heidenreich at the Máxima and prof. dr. Irmela Jeremias at KiTZ will look for a way to deliver MLL/AF4-targeted treatment into the bone marrow in mice, which could pave the way for a precision medicine approach for childhood acute lymphoblastic leukemia (ALL).
Prof. dr. Monique den Boer at the Máxima and dr. Ashok Kumar Jayavelu will bring together DNA, RNA and protein information about ALL, which could in future lead to refined diagnosis and new targets for therapy.
A team led by prof. dr. Max van Noesel, dr. Claudia Janda, prof. dr. Jan Molenaar and dr. Marcel Kool at the Máxima together with dr. Ina Oehme and dr. Olaf Witt at KiTZ aims to improve personalized medicine for childhood cancer.