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Division of Pediatric Neurooncology

Prof. Dr. Stefan Pfister

Intratumoral heterogeneity demonstrated by amplification of distinct oncogenes (red= MYCN, green = GLI2) in different cell populations of a medulloblastoma sample.
© dkfz.de

Pediatric Neurooncology is currently a vibrant field of research. This is desperately needed, since brain tumors have become the number one cause of cancer-related mortality in children. Our group aims to bridge the gap between generating genomic screening data as well as faithful models for preclinical drug testing, and exploiting these data for the sake of our patients. The first goal includes the identification, validation and clinical application of prognostic and predictive biomarkers in different childhood brain tumors, including genome, transcriptome and epigenome analysis, and integrative bioinformatics approaches. The second major focus involves the generation of suitable in vitro and in vivo models for systematic pre-clinical testing of novel smart drugs, often in combination with established cytotoxic drugs, chemotherapy or immunotherapy. These novel therapies are ultimately translated into patient care, tightly linked with thorough patient selection based on the genetic/molecular signature of the individual tumor (“personalized cancer care”).

FUTURE OUTLOOK
The thorough understanding of the immense biological heterogeneity of childhood brain tumors is a prerequisite for targeted treatment approaches. Thus, we will continue to comprehensively investigate the entire genetic and epigenetic diversity of childhood brain tumors within and across histopathological entities. Many of these novel methods are currently being prepared for routine diagnostic applications in a clinical setting through our nationally and internationally acting molecular diagnostics programs (www.pediatric-neurooncology.com). Preclinical models will allow us to specifically test biological hypotheses gained from genome-wide primary tumor analyses in vitro and in vivo, before they are recommended for use in patients. Another focus will be the analysis of clonality within tumors, their respective metastases, and tumor relapses, by ultra-deep next-generation and single-cell sequencing techniques. As a third major focus, we have started focusing on the detection of tumor-specific alteration in body fluids, such as cerebrospinal fluid and plasma, which can be exploited for molecular diagnostics, tumor cell clearance (minimal residual disease), detection of molecular targets, and primary resistance mechanisms. Finally, we will evaluate novel as well as many conventional therapies systematically for their inter-individual range in pharmacokinetics. These differences might help explaining successes and failures in individual patients.

Contact

Prof. Dr. Stefan Pfister
Pediatric Neurooncology (B062)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 424618

Selected Publications

  • Lin, C.Y., Erkek, S. et al., …and Pfister, S.M.*, Bradner, J.E.*, Northcott, P.A.* (2016). Active medulloblastoma enhancers reveal subgroup-specific cellular origins. Nature. 530(7588):57-62.
  • Pajtler KW, Witt H, Sill M et al., …and Kool, M.*, Pfister, S.M.* (2015). Molecular Classification of Ependymal Tumors across All CNS Compartments, Histopathological Grades, and Age Groups. Cancer Cell. 27(5):728-43.
  • Northcott, P. et al., …and Peter Lichter, P.*, Korbel, J.O.*, Wechsler-Reya, R*, Pfister, S.M.* (2014) Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma. Nature 511(7510):428-34.
  • Kool M et al.,…,and Wechsler-Reya, R.J.*, Lichter, P.*, Pfister, S.M*. (2014). Genome Sequencing of SHH Medulloblastoma Predicts Genotype-Related Response to Smoothened Inhibition. Cancer Cell 25(3):393-405.
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