Learning from neuroblastoma about how to treat cancerous tumors

Cancer is difficult to cure because it is a complex disease. The inherited background and basic characteristics of each patient in addition to environmental conditions that the patient is exposed to influence how tumor cells develop and spread in a dynamic process. Where the tumor is, what types of cells surround it and what state the biochemical molecules that control tumor cell function are in, meaning the genes and their controlling elements as well as products of the genes that actively regulate cell function, also influence how tumor cells develop and spread. Since these all differ in each patient, individualized therapies based on „biomarkers“ and „molecular signatures“ that can be identified using new technologies could make new strides in treating cancer. It is now possible to obtain these kinds of data using „high-throughput“ processes that carry out large numbers of detections in parallel. It has been difficult to make full use of the knowledge acquired by these methods to create new diagnostics and treatments. A new analytical approach combining medical, biological, biochemical and computer science research to try to learn about a whole system, calle systems medicine has the power to more efficiently use and learn from high-throughput data. This is where the joint project, “TERMINATE-NB: From Cancer DiagnOMICS to Precision Medicine: Model Neuroblastoma”, funded by BIH and under the guidance of Prof. Dr. Angelika Eggert (Charité) and Prof. Dr. Matthias Selbach (MDC), comes into play. Neuroblastoma is being used as a model disease to build a concept for characterizing tumors integrating all available molecular data that identifies and supports development of new diagnostic and treatment approaches to treat this and other cancers.

Neuroblastoma is a cancer of components of the nervous system that are outside the brain, and mostly affects children. It progresses very differently in individual patients. While minor forms frequently heal spontaneously without any treatment at all, serious forms of the disease are often deadly. The tumors responsible for these deadly cases are what makes this kind of cancer interesting for research purposes, since only very few genes are mutated. Most cancers that strike adults have acquired many more mutation in their genes, making looking for the cause a little like looking for the proverbial needle in the haystack. The search for the genetically-determined causes of the disease is simplified in neuroblastoma. In-depth molecular research of a tumor is highly sensitive to differences in treatment or timing of when the tumor samples were obtained. Since diagnosis and treatment of neuroblastoma is highly standardized in Germany, with more than 99% of patients involved in the national trial and parents are strongly supportive for allowing patient samples to be used in research, researchers are able to draw on comprehensive and well-documented patient samples for their analyses. These samples will be used in the project to identify and understand the central signaling networks responsible for typical characteristics of the highly aggressive neuroblastoma tumor cells. The researchers receiving the funding want to analyze mutations that occur in genes, and develop a better understanding of the differing behavior of the tumor cells harboring the mutant genes.

“We now have the opportunity to reach a new milestone in cancer treatment with the best scientific and technological procedures. Neuroblastoma is the perfect model disease to analyze molecular mechanisms, understand them with systems medicine approaches, and transfer this knowledge not only to clinical use for neuroblastoma patients, but the whole discovery system to other cancer types,” says principal investigator Angelika Eggert. She is the director of the Department of Pediatrics, Division of Oncology and Hematology at Charité; Matthias Selbach is the head of the MDC’s “Proteome Dynamics” research group. He has established technologies there to systematically characterize whole networks of proteins in tumor cells. “Together with the other Core Facilities at the BIH, including the Bioinformatics Core, we will be able to gain an overview of the relevant processes on all levels for the first time,” says Matthias Selbach. The project will run from August 2015 until July 2019, and the research will be carried out in a total of eight interdisciplinary sub-projects with 27 scientists from the MDC and Charité.

Collaborative joint projects (collaborative research grants) at BIH
Berlin Institute of Health funds the joint, interdisciplinary projects of Charité and MDC basic research scientists and clinicians. A decisive factor in the granting of funds is a systems medicine approach with clear translation prospects. The collaborative research grants are one of the two instruments developed for research funding. They provide funding for larger, long-term joint projects with up to eight sub-projects. The applications were reviewed by an external committee of experts. Collaborative research grants are funded for a period of four years. More information on the joint projects can be found online (www.bihealth.org/en/research/research-projects).

About Berlin Institute of Health (BIH)
Berlin Institute of Health (BIH) was founded in March 2013. It brings together Charité – Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine (MDC) with the objective of advancing translational medicine based on a systems medicine approach and via the accelerated transfer of research findings into clinical application, and the channeling of clinical findings back into basic research. As of the beginning of April 2015, BIH is an autonomous entity under public law; Charité and MDC are independent, member entities within this. With new scientific and technological developments in biomedicine, the institute will create new diagnostic, therapeutic, and preventive approaches in medicine and therefore for public health.

Contact:
Alexandra Hensel
Head of Communications
Berlin Institute of Health (BIH)
Kapelle-Ufer 2 | 10117 Berlin | Germany
Pone +49 (0)30 450 543019
Fax +49 (0)30 450 7543999
hensel@bihealth.de

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