The area "Early Cancer Diagnostics" is a major focus of the research group under the direction of Dr. med. Kristian W. Pajtler. Here we examine so-called Liquid Biopsy samples (liquid biopsies) from blood and other liquid components of the body, such as liquor or urine, to gain information about the respective cancer.

For this, genetic material from, for example, circulating tumor cells is isolated and examined using modern methods of genetic analysis in order to recognize early changes in the cancer cells and to closely monitor the development of the disease. In the future, these techniques could potentially be used for therapy control, but also for the follow-up of former cancer patients. With very few exceptions, Liquid Biopsy-based analyzes are not yet routine and are therefore currently only used in clinical trials.

In "Early Cancer Diagnostics", we also investigate genetic alterations which might depict predispositions to the development of cancer. Amongst others, our examinations include the bioinformatic analysis of large groups of pediatric cancer patients to identify previously unknown relevant genetic changes, the collaboration with the "Genetic Cancer Predisposition" working group of the GPOH and the Pediatric Cancer Working Group of the AACR in order to develop recommendations for the early detection and monitoring of affected patients. Another field of activity is the accompanying research in the context of the Li-Fraumeni syndrome / cancer predisposition syndrome register. Li-Fraumeni syndrome (LFS) is an autosomal dominant disease that is based on a germline mutation of the tumor suppressor gene TP53. TP53 encodes the protein p53, which protects the cell from a variety of stressors. The loss of p53 leads to a very high risk for hematologic and solid cancers in affected individuals, which often occur for the first time in childhood.

Within the research area "Reverse Translation", experimental procedures performed in the laboratory are based on knowledge and experience gained in the clinic. Using this approach, we try to identify new mechanisms of tumorigenesis and recapitulate them in the model. From this we hope to derive findings for a more accurate diagnosis and better therapy of future patients. For example, we have developed models for different molecular groups of childhood brain tumors that can be used to test new therapeutic approaches in the future.

In addition, in cooperation with the Department of Clinical Pharmacology of the University Hospital Heidelberg (Prof. Haefeli), we are developing new methods for the individualized treatment of brain tumor patients. For this purpose, the concentration of certain drugs is measured both in the blood and in the tumor. By this, we hope to, for example, answer the frequently discussed question whether the permeability of the barrier which normally protects the brain from toxic substances (blood-brain barrier) increases due to the cancer and the treatment, allowing the drugs to work better. For a variety of medications it has not been established if they can cross the intact barrier at all, while others were already designed not to reach the brain out of concern that they might cause neurological side effects. The aim of this research is to optimize tumor therapy and, at the same time, to reduce therapy-related side effects.

Of particular interest to the group is the research of ependymomas, a heterogeneous group of brain tumors. The classification of these tumors using classical histopathology is often a major challenge, and even experienced neuropathologists sometimes come to different assessments in the diagnostic evaluation of the same tumor. In cooperation with the group "Preclinical Research" (Dr. M. Kool), we have established a new molecular classification system that allows a more precise diagnosis and risk assessment. One of the new molecular subgroups has already been adopted by the WHO in the updated version of the classification of brain tumors.

One of the main tasks of the group is the further translation of these findings into the clinic. It is already broadly accepted that molecular classification will be used in all clinical studies with ependymal patients in the future. Despite intensive research, in contrast to other brain tumor entities, no genetic mechanisms contributing to tumorigenesis and / or its progression have been identified for most molecular groups of ependymomas. We are, therefore, pursuing the strategy of identifying regulatory enhancer elements within the genome (so-called enhancers and superenhancers, which lead to an increased expression of the gene when activated) by analyzing active chromatin regions in order to discover crucial networks and therapeutically relevant target molecules. Especially ependymomas of the posterior fossa (PF-EPN-A) occuring in small children represent a clinical challenge because they are aggressive tumors with a high risk of relapse. Together with major international centers, we are currently investigating whether these tumors can be further subdivided molecularly in order to more quickly discover suitable approaches for targeted therapies in these tumors.

Together with the groups "Pediatric Glioma Research" (Dr. D. Jones) and "Clinical Bioinformatics" (Dr. N. Jäger) and the Clinical Cooperation Unit Pediatric Oncology (Prof. O. Witt) we are closely involved in the INFORM project (INdividualized Therapy for Relapsed Malignancies in Childhood). INFORM is an international initiative that uses high-throughput sequencing technology to create personalized molecular tumor profiles of patients with progressive or reoccurring cancer. The information on potential targets should enable physicians to offer a customized therapy approach using new targeted drugs. The tasks of our group lie primarily in the internationalization of the study as well as in the areas of data, project and clinical management.