NCT Research

Clinical Cancer Research Program in Pediatric Oncology

Expertise

The Pediatric Oncology Program covers the whole spectrum of the field ranging from mechanistic molecular driven research to disease oriented translational projects up to clinical research conducting phase I-III trials including evaluation of innovative personalized oncology strategies. The CCRP Pediatric Oncology enrolls >95% of all patients in national and international multi-center trials as part of their routine patient care. The program has a strong clinical and translational focus on T-cell leukemia, osteosarcoma, brain tumors and stem cell transplantation. Patients are treated in multidisciplinary teams including radiation oncology applying state-of-the art treatment options.Through tight collaboration with the German Cancer Research Center (DKFZ) and the European Molecular Biology Laboratory (EMBL) basic science discoveries are translated into clinical practice including personalized treatment strategies based on next generation sequencing.

CCRP Pediatric Oncology
 

  • Department of Pediatric Oncology, Hematology, Immunology and Pneumology
  • Section of Pediatric Radiology, Department of Diagnsotic Radiology
  • Department of Pediatric Neuroradiology
  • Department of Nuclear Medicine
  • Department of Radiooncology
  • Department of Pathology and Neuropatholoy
  • Section of Pediatric Surgery, Department of General Surgery
  • Department of Urology
  • Department of Neurosurgery
  • NCT Clinical Trial Center

  • Department of Pediatric Oncology/MMPU (Prof. Dr. A. Kulozik, Prof. Dr. M. Muckenthaler)
  • Division CCU Pediatric Oncology/DKFZ (Prof. Dr. O. Witt)
  • Division Pediatric Neurooncology/DKFZ (Prof. Dr. S. Pfister)
  • Department of Neuropathology (Prof. Dr. A. van Deimling)
  • Division Molecular Genetics/DKFZ (Prof. Dr. P. Lichter)

  • Generation of novel mouse models of iron overload (Prof. Dr. M. Muckenthaler et al)
  • Functional analyses of iron regulatory mechanisms and cancer (Prof. Dr. M. Muckenthaler et al)
  • Neuropath 2.0 - Increasing diagnostic accuracy in pediatric neurooncology (Prof. Dr. S. Pfister et al.)
  • Pediatric glioblastoma: Mutation specific cellular screen of a compound library (Dr. P. Johann, Prof. Dr. S. Pfister)
  • Characterization of Histondeacetylase-Isoform driven oncogenesis and development of  selective inhibitors (Prof. Dr. O. Witt, Dr. I. Oehme, Dr. Till Milde, Dr. H. Deubzer)
  • Pediatric Targeted Therapy (Dr. T. Milde, Prof. Dr. O. Witt, Prof. Dr. S. Pfister, Prof. Dr. A. van Deimling)
  • Development of molecular subgroup specific models in pediatric neurooncology (Dr. T. Milde, Prof. Dr. O. Witt, Prfo. Dr. S. Pfister)
  • Generation of a novel BRAF-fusion pediatric low grade glioma human and mouse model (Prof. Dr. O. Witt, Dr. T. Milde, Dr. F. Selt, Prof. Dr. S. Pfister)

  • Schwerionenradiotherapie bei Patienten mit einem inoperablen Osteosarkom,  OSCAR Studie, Dietmar Hopp – Stiftung (Kulozik)
  • Virtual Liver Network Verbundprojekt, TP D3, BMBF (Muckenthaler);
  • Validation of biomarkers for personalized cancer medicine, TP5, BMBF (Muckenthaler);
  • Translationale Medizin der Hereditären Anämien, Dietmar Hopp-Stiftung (Muckenthaler)
  • SFB 1036, TP 16, DFG (Muckenthaler)
  • Macrophage iron recycling or dietary iron uptake?, Universität Heidelberg, Innovationsfonds Frontier (Muckenthaler)
  • EcTop 5 nc RNAs, Universität Heidelberg, Excellenzcluster CellNetworks (Muckenthaler)
  • Use of cerebrospinal fluid genetics for the diagnosis subgrouping and minimal residual disease monitoring in medulloblastoma, James S McDonnell Foundation (Pfister)
  • Molecula characterization and targeted therapy ofrecurrent Medulloblastoma, Deutsche Kinderkrebsstiftung (Pfister)
  • ICGC Pedbrain Tumor, Genomic Analysis of pediatric brain tumors, BMBF (Pfister, Lichter, Eils)
  • Württembergischer Krebspreis (Cancer Award), Dres. Bayer Foundation (Pfister)
  • e-Med: Cancer TelSys, BMBF (Pfister)
  • e:BIO MYC-NET, BMBF (Pfister)
  • Phase I/II study of vorinostat in children with relapsed or refractory solid tumor, leukemia, and lymphoma, Deutsche Kinderkrebsstiftung (Witt)
  • Molecular characterization and therapy of recurrent medulloblastoma, Deutsche Kinderkrebsstiftung (Pfister, Witt, Milde)
  • MycNet Verbundprojekt, TP5, BMBF (Witt, Milde)
  • Modellierung der in vivo Pharmakokinetik in der 3D-Tumorzellkultur zur besseren Vorhersehbarkeit einer klinischen Antwort für neue anti-tumorale Wirkstoffe, Bundesministerium für Wirtschaft und Technik (Witt, Oehme)
  • EXIST1-Studie, Novartis (Witt)
  • Purification of HDAC complex from Mammalian Cells and Small-Scale Substrate Screen with putative HDAC11-selective inhibitors, DKFZ-Bayer-Alliance (Deubzer, Witt)

Our group/department has:

  1. Discovered the first histone mutation in cancer, namely in childhood glioblastoma (Schwartzentruber et al., Nature 2012) and described a molecular classification of glioblastoma (Sturm et al., Cancer Cell 2012), medulloblastoma and ependymoma (EP) (Korshunov et al., J Clin Oncol  2010a, 2010b; Remke et al., J Clin Oncol  2011; Witt et al., Cancer Cell 2011)
  2. Initiated and currently coordinate phase I-III clinical trials including the first multicenter, nationwide study on personalized pediatric oncology (INFORM) and the Pediatric Targeted Therapy (PTT) program for individualized pathway analysis in relapsed pediatric tumors .
  3. Described novel druggable oncogenic pathways involving HDACs isoforms (Oehme et al. PNAS 2013, Lodrini et al. Nucl Acid Res 2013) resulting in phase I/II clinical trial of an HDAC inhibitor in children.
  4. Identified a novel architecture of a new class of 3’ end mRNA processing signals, which govern stress induced upregulated 3’ end mRNA processing a novel mechanism of tumor spread (Danckwardt et al. Molecular Cell 2011; Hollerer et al. EMBO Molecular Medicine 2013).
  5. Established a special counseling clinic for anemia and iron-related disorders. We identified novel disease entities related to a misregulation of iron metabolism (Cozzi et al., J Exp Med 2013) and unravelled critical pathways for maintaining balanced iron homeostasis (Castoldi et al., J Clin Invest 2011; Mleczko-Sanecka et al., Blood 2010)

  • Initiation and coordination of early clinical trials applying targeted therapy and personalized approaches in pediatric oncology based on molecular understanding of pediatric cancer biology
  • Preclinical and clinical development of novel treatment strategies of osteosarcoma  Molecular characterisation of leukemogenic pathways and of mechanisms that govern the clonogenic evolution and the clone selection during the progression of pediatric T-lymphoblastic leukemia
  • Translation of ICGC results on low grade glioma and medulloblastoma into novel molecular based risk stratification systems and targeted therapies
  • Development of novel epigenetically active targeted compounds towards early clinical trials in collaboration with pharma

  1. Jones DT, Hutter B, Jäger N, Korshunov A, Kool M, Warnatz HJ, Zichner T, Lambert SR, Ryzhova M, Quang DA, Fontebasso AM, Stütz AM, Hutter S, Zuckermann M, Sturm D, Gronych J, Lasitschka B, Schmidt S, Seker-Cin H, Witt H, Sultan M, Ralser M, Northcott PA, Hovestadt V, Bender S, Pfaff E, Stark S, Faury D, Schwartzentruber J, Majewski J, Weber UD, Zapatka M, Raeder B, Schlesner M, Worth CL, Bartholomae CC, von Kalle C, Imbusch CD, Radomski S, Lawerenz C, van Sluis P, Koster J, Volckmann R, Versteeg R, Lehrach H, Monoranu C, Winkler B, Unterberg A, Herold-Mende C, Milde T, Kulozik AE, Ebinger M, Schuhmann MU, Cho YJ, Pomeroy SL, von Deimling A, Witt O, Taylor MD, Wolf S, Karajannis MA, Eberhart CG, Scheurlen W, Hasselblatt M, Ligon KL, Kieran MW, Korbel JO, Yaspo ML, Brors B, Felsberg J, Reifenberger G, Collins VP, Jabado N, Eils R, Lichter P, Pfister SM. Recurrent alterations in FGFR1 and NTRK2 represent novel therapeutic targets in childhood astrocytoma. Nat Genet. 2013 Aug; 45(8):927-32.….
  2. Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tönjes M, Sill M, Bender S, Kool M, Zapatka M, Becker N, Zucknick M, Hielscher T, Liu XY, Fontebasso AM, Ryzhova M, Albrecht S, Jacob K, Wolter M, Ebinger M, Schuhmann MU, van Meter T, Frühwald MC, Hauch H, Pekrun A, Radlwimmer B, Niehues T, von Komorowski G, Dürken M, Kulozik AE, Madden J, Donson A, Foreman NK, Drissi R, Fouladi M, Scheurlen W, von Deimling A, Monoranu C, Roggendorf W, Herold-Mende C, Unterberg A, Kramm CM, Felsberg J, Hartmann C, Wiestler B, Wick W, Milde T, Witt O, Lindroth AM, Schwartzentruber J, Faury D, Fleming A, Zakrzewska M, Liberski PP, Zakrzewski K, Hauser P, Garami M, Klekner A, Bognar L, Morrissy S, Cavalli F, Taylor MD, van Sluis P, Koster J, Versteeg R, Volckmann R, Mikkelsen T, Aldape K, Reifenberger G, Collins VP, Majewski J, Korshunov A, Lichter P, Plass C, Jabado N, Pfister SM. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma. Cancer Cell. 2012 Oct 16;22(4):425-37
  3. Oehme I, Linke JP, Böck BC, Milde T, Lodrini M, Hartenstein B, Wiegand I, Eckert C, Roth W, Kool M, Kaden S, Gröne HJ, Schulte JH, Lindner S, Hamacher-Brady A, Brady NR, Deubzer HE, Witt O. Histone deacetylase 10 promotes autophagy-mediated cell survival. Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):E2592-601
  4. Danckwardt, S. A.S. Gantzert, S. Macher-Göppinger, H. C. Probst,, M. Gentzel, M. Wilm, H.J. Gröne, P. Schirmacher, M.W. Hentze, A.E. Kulozik. p38 MAPK controls prothrombin expression by regulated 3’end processing: implications for the acute phase response and tumour progression. Molecular Cell 41: 298–310 (2011).
  5. Castoldi M, Vujic Spasic M, Altamura S, Elmén J, Lindow M, Kiss J, Stolte J, Sparla R, D'Alessandro LA, Klingmüller U, Fleming RE, Longerich T, Gröne HJ, Benes V, Kauppinen S, Hentze MW, Muckenthaler MU. J Clin Invest. 2011 Apr;121(4):1386-96.