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Zentrum für Kinder-und Jugendmedizin / AG Faber

Hepatoblastoma (HBL) is the most common primary liver tumor in children, and is usually diagnosed during the first 3 years of life. Multimodal therapy, which consists of complete surgical resection plus liver transplantation and chemotherapy, has led to improved outcomes for children with HBL. However, relapse after transplantation may occur and are generally lethal.

The research group of Professor Faber is interested in developing new therapeutic approaches based on the modulation of signal pathways deregulated in HBL. As model, primary cells isolated from HBL patients are used. A particular focus of the group is the insulin-like growth factor (IGF) pathway. IGF has long been recognised as a major molecular target in paediatric and adult tumour entities, but no inhibitors have been released to date. Our group has shown that the IGF pathway can be inhibited off-target by using ceritinib alone or in combination with dasatinib in personalised therapy protocols (PMID: 32224911, PMID: 31480400, PMID: 31234291). First results indicate that this combination can be effective also in HBL (Figure). Due to the re-activation of several embryonic pathways in HBL, further analysis should clarify which other pathways are being recruited that compensate for IGF inhibition.

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Primary tumor cells of a HBL patient were stimulated with IGF2 (orange), inducing cell proliferation. The proliferation was ihnibited by the combination of ceritinib and dasatinib. Analysis was done using the live cell analysis system xCELLigence.


Another Focus of the Group is the immunotherapy of pediatric tumors. While immunotherapy is changing the therapeutic landscape of adult patients, few immunotherapies have been released for pediatric patients and few clinical studies are enrolling pediatric patients. In this setting, monoclonal antibodies may be employed to specifically direct immune responses toward tumor HBL cells. We are currently developing in vitro co-culture assays to analyze the interaction between tumor and immune cells and are interested in the identification of suitable targets for monoclonal antibodies. In this context, we are characterizing the composition of tumor infiltrating immune cells in pediatric tumors, particularly of non-conventional T cells (PMID: 32973759).

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Sprecher:

Univ.-Prof. Dr. med. Peter R. Galle
I. Medizinische Klinik und Poliklinik


Koordinatorin:

Ivonne Dietzel
Mainz Research School of Translational Biomedicine (TransMed)

Das Kolleg wird von der Else Kröner-Fresenius-Stiftung gefördert.

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