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Laboratory research

Information on the projects that are performed at the Research Laboratory of Pediatric Oncology

Biological determinants of leukemogenesis and treatment outcome and development of targeted therapies in childhood cancer

Head:
Prof Dr Rob Pieters

Working group leaders:
Dr Monique den Boer
Dr Jules Meijerink
Dr Max van Noesel
Dr Marry van den Heuvel-Eibrink
Dr Ronald Stam
Dr Michel Zwaan


The pediatric oncology research program focuses on the following aims:

• Developing clinically and biologically relevant classification of childhood cancers,
   especially leukemia. This is done by genome-wide screening techniques at the DNA
   level (array CGH, whole genome and candidate gene DNA sequencing), at the RNA
   level (gene expression and microRNA profiling) and at the protein level (phosphoproteomics,
   kinase assays) of cancer cells. In addition, serum and cerebrospinal fluid of
   patients is analysed for aberrant proteins and other factors that may serve as
   (bio)markers for diagnosis and efficacy of treatment.
• Identification of (epi)genetic abnormalities involved in the development of genetic
   subtypes of leukemia and solid tumors including brain tumors in children. Especially the
   role of silencing of tumor suppressor genes by methylation is analysed.
• Identification of molecules associated with chemotherapy resistance. New resistance
   genes are identified by comparing gene expression profiles of therapy resistant and
   sensitive patients which is confirmed by other techniques. New strategies to modulate
   the effects of these resistance genes are developed by functional studies.
• Studying the contribution of the local bone marrow environment to leukemic cell survival
   and drug responsiveness. Factors released by leukemic cells and bone marrow-derived
   mesenchymal cells are being analysed for their potential to stimulate the survival,
   proliferation and drug resistance of leukemic cells. Interference with the leukemiamicroenvironment
   interaction is studied for the potential to optimize the effect of
   chemotherapy.
• Identification of new therapeutic targets and development of new treatment strategies for
   children with cancer. New targets are identified and confirmed by techniques described
   above in specific subgroups of patients. This is followed by validation studies to define
   the effect of inhibition of the target genes, a.o. by RNA interference. The efficacy of new
   drugs directed against these targets is tested in preclinical models.
• Following this preclinical phase, new drugs are tested in clinical phase I and II studies in
   children. The Department of Pediatric Oncology of the Erasmus MC-Sophia Children’s
   Hospital is part of the European ITCC (Innovative Therapies for Children with Cancer)
   network to perform these studies. The research laboratory of Pediatric Oncology is
   responsible for the preclinical studies in especially leukemia in this consortium and plays
   a leading role in early clinical phase I/II studies.
• The clinical part of the program includes also: (1) Phase III studies in pediatric oncology;
   (2) Improvements in supportive care, late effects of treatment and quality of life.
   The ultimate goal of the research program is to develop targeted therapies for children with
   cancer. This should lead to more effective and less toxic treatment strategies for biologically
   defined classes of patients. The program is mainly directed to children with hematological
   malignancies but includes also to brain tumors and solid tumors.


Research working groups (please use the link when you want more information):

Overall supervisor of the research programProf. Rob Pieters, head Dept. of Pediatric Oncology
  
Working Group LeadersFor further information on the projects click here 
 Monique L. den Boer, PhD, Assoc Prof. ALL  
 Jules P.P. Meijerink, PhD, Assoc Prof.  T-cell ALL  
 Ronald W. Stam, PhD  Infant ALL 
 Max M. van Noesel, MD, PhD  Solid tumors 
 Marry M. van den Heuvel-Eibrink, MD, PhD, Assoc Prof.  AML and MDS  
 C. Michel Zwaan, MD, PhD, Assoc Prof.  AML and MDS  
 Erna M.C. Michiels, MD, PhD  Brain tumors