Developmental Origins of Pediatric Cancer

DKFZ Junior Group Developmental Origins of Pediatric Cancer

Dr. Lena Kutscher

Neuronal progenitors migrate out of the early rhombic lip.
© dkfz.de

Cancer is a disease caused by abnormal, uncontrolled cell division. In adults, external factors, such as lifestyle choices, environmental exposures, or occupational hazards commonly contribute to tumorigenesis. In children, however, these external factors play a smaller role. Instead, pediatric cancer is thought to arise from a block of developmental maturation. Therefore, effectively treating pediatric cancer will require a thorough knowledge of normal development, including the cellular function of the genes involved. For example, in medulloblastoma, a highly aggressive embryonal brain tumor, a differentiation block in distinct progenitor cell types gives rise to fo¬ur tumor subgroups. Each subgroup has its own clinical features, prognosis, and treatment options. Although 70% of diagnosed children survive over five years, current treatments severely compromise quality of life. Learning more about medulloblastoma disease modalities in relation to their developmental origins will guide patient-specific treatment, increasing remission rates and reducing long-term toxicity.

Researchers have identified probable genetic causes using -omic analyses of patient samples. However, rigorous functional validation of putative disease-causing genes and the corresponding cell states is still required. By studying basic neural development, we may better understand pediatric tumor initiation and progression. Our group’s long-term goal is to understand normal cerebellum development and elucidate the progression to malignancy. Ultimately, we want to develop mechanism-of-action-based treatments with reduced toxicity for children with brain tumors.

Contact

Dr. Lena Kutscher
Developmental Origins of Pediatric Cancer (B430)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 580
69120 Heidelberg
Tel: +49 6221 42 4622

Selected Publications

  • Okonechnikov, K, Pfister, SM, Kutscher, LM. (2019) Probing medulloblastoma initiation at the single-cell level. Trends Cancer 5:12, 759-761
  • Kutscher LM, Keil W, Shaham S. (2018) RAB-35 and ARF-6 GTPases Mediate Engulfment and Clearance Following Linker Cell-Type Death. Dev. Cell 47: 222–238.e6
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