Zeroing in on neuroblastoma: Division of Evidence-Based Medicine (dEBM) - Charité

New collaborative research center at Charité

Vielzahl eng beieinander liegender Zellen, die grün angefärbt sind und in der Mitte einen blau angefärbten Zellkern haben. — Neuroblastoma cells (green) in the adrenal gland. Cell nuclei are shown in blue. © Charité | Anja Heeren-Hagemann

Neuroblastoma is the third most common form of malignant cancer in pediatric patients. Chances of cure vary widely. In advanced cases, tumors often develop resistance to treatment and have already metastasized by the time the disease is diagnosed. To improve treatment options for children with high-risk neuroblastoma, researchers have now teamed up under the leadership of Charité – Universitätsmedizin Berlin in a collaborative research center called Decoding and Targeting Mechanisms of Neuroblastoma Evolution to take a closer look at how tumors like these arise and develop over time. The German Research Foundation (DFG) has pledged about 13.5 million euros in support of the project, initially for a term of just under four years.

In neuroblastoma, tumors frequently develop in the abdomen or along the spinal column. The tumors form when certain cells in the nervous system degenerate very early on in the body’s development – possibly even before birth. This is why the cancer is most prevalent in children under the age of six years and is sometimes even found in newborns. It is characteristic of neuroblastomas to have a wide range of clinical presentations, with the disease also taking different courses. Some tumors spontaneously subside, while others grow very aggressively. The aggressive forms can often be treated successfully at the start, but are prone to relapses and often spread to other organs. For this reason, more than half of children with high-risk neuroblastoma do not survive, even with modern medicine.

“To give these kids a better chance of beating the disease, we need to better understand what exactly occurs in tumor tissue in the course of treatment,” says Prof. Angelika Eggert, Director of the Department of Pediatric Oncology and Hematology at Charité and the spokesperson of the collaborative research center, which has now been approved for three years and nine months. “As soon as we know what drives evolution in neuroblastoma, we plan to develop targeted new combination treatments. Our goal for the future is to be able to predict for each individual case how the disease will progress and then use precision therapies to keep the tumor from relapsing.”

The researchers assume that various cell types in the tissue of each neuroblastoma change their properties in different ways when they are exposed to cancer drugs or move to other areas of the body. “Contrary to previous assumptions, new findings indicate that the tumor cells not only evolve genetically, meaning they do not only accumulate errors in the genetic material,” says Eggert, who is also the spokesperson for the Berlin site of the German Cancer Consortium (DKTK) and co-director of the National Center for Tumor Diseases (NCT) in Berlin. “Instead, there are evidently additional non-genetic factors that affect the behavior of tumor cells, such as chemical changes to proteins.”

To study this unusually complex process of tumor development in detail, the research alliance plans to analyze neuroblastoma tissue in depth, cell by cell. The researchers hope to use the latest methods to catalog what happens in the tumor cells at the DNA, RNA, epigenetic, and protein levels. They also plan to use artificial intelligence in the next step to help identify new lines of attack for targeted combination therapy. To this end, the research alliance has brought together interdisciplinary and interinstitutional expertise from researchers at Charité, the Berlin Institute of Health at Charité (BIH), the Max Delbrück Center, the University of Cologne, Julius-Maximilians-Universität of Würzburg (JMU), the University of Tübingen, and the German Cancer Research Center (DKFZ).

Eggert firmly believes that an interdisciplinary and cross-institution approach that combines high-level clinical and scientific expertise with advances in technology and data science is the most promising path forward when it comes to developing new treatment strategies, not only for neuroblastoma, but also for other complex diseases.

DFG collaborative research centers
Collaborative research centers allow researchers to tackle innovative, challenging, and long-term research projects as a group, thereby supporting the further development of core areas and structures at the applicant universities. To receive funding, the projects must demonstrate high scientific quality and originality on an internationally competitive level and be supported by outstanding researchers. Financing is provided for a maximum of 12 years. The collaborative research centers that have now been approved are scheduled to start their projects on October 1 of this year.