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The mission of the division of "Translational Pediatric Sarcomas Research", which corresponds to the DKFZ division of the same name, is to improve treatment options for children and adolescents affected by sarcomas. We aim at uncovering disease mechanisms that can be used diagnostically and therapeutically to improve the long-term chances of recovery of our young patients. The focus lies on new methods that are essential for correct diagnosis and the choice of the best possible therapy. We also investigate less aggressive therapies and new approaches to overcome drug resistance of tumors. In this regard, one special objective is to decipher the interactions between acquired mutations and innate natural variants of the genome, which can play a decisive role in the development and progression of cancer, particularly in Ewing sarcoma.
We aim at developing novel therapeutic strategies based on new insights into the molecular mechanisms of disease following two major lines of research (see research areas). Our investigations start with the analysis of the patients’ tumors in situ, followed by studying patient-derived cell lines using a wide variety of in silico, in vitro, and in vivo techniques.
The division is supported by the Barbara und Wilfried Mohr Stiftung.
Histology, omics‘-analyses, preclinical models, correlation with clinical data
Dominant oncogenes often hijack or interfere with developmental pathways thereby conferring a considerable growth advantage to tumor cells. We are interested in the mechanisms through which oncogenes arrest sarcoma cells in a lineage-specific, early-committed but yet largely undifferentiated state via deregulation of key developmental pathways, and how they cooperate with them to promote tumorigenesis and cancer progression.
Primary and/or secondary resistance to conventional chemotherapeutic drugs is a frequent event in pediatric sarcoma. Chemo-resistance is a highly specific process in which tumors become resistant to certain drugs while maintaining (limited) susceptibility toward others. Underlying to this resistance is considerable plasticity due to intra-tumor heterogeneity, which enables the adaptation to therapeutic stress on the clonal and sub-clonal level. We strive for illuminating the genetic basis and biological mechanisms of tumor-heterogeneity and aim at identifying novel biomarkers for individualized risk-stratification, prediction of treatment response, and to indicate which targeted therapeutics may help overcoming resistance to conventional (chemo)therapeutics.
The team Translational Genomics (T. Grünewald) systematically established multi-dimensional omics-datasets of a large number of pediatric sarcomas and correlates identified molecular alterations with clinical data to identify novel driver mutations, druggable targets and prognostic/predictive biomarkers, and to create resources for hypothesis generation and functional validation.
Contact:
Univ.-Prof. Dr. Dr. Thomas Grünewald
Phone: +49 6221 42 3718
E-Mail: t.gruenewald(at)dkfz-heidelberg.de
The team Mechanisms of Cancer Progression (F. Cidre-Aranaz) aims at deconvoluting the multilayered process underlying cancer progression and metastasis. We employ systems biology approaches combining in vitro and in vivo functional characterization of potential targets with multi-omics data and clinical information to identify targetable vulnerabilities in pediatric sarcomas.
Contact:
Dr. Florencia Cidre-Aranaz
Phone: +49 6221 42 3717
E-Mail: florencia.cidrearanaz(at)dkfz-heidelberg.de
The team Innovative Therapies (S. Ohmura) investigates potential therapeutic targets for pediatric sarcomas through comprehensive analyses crossing omics and clinical data sets. Our scope lies in developing targeted approaches with a particular emphasis on therapy-refractory tumors, which may enable more effective therapies with less adverse effects.
Contact:
Dr. Shunya Ohmura
Phone: +49 6221 42 3717
E-Mail: shunya.ohmura(at)dkfz-heidelberg.de
More information about the team can be found on the DKFZ website.
t.gruenewald(at)kitz-heidelberg.de
Postal address:
Deutsches Krebsforschungszentrum (DKFZ)
Div. Translational Pediatric Sarcoma Research/B410
Im Neuenheimer Feld 280
69120 Heidelberg
Overview of all scientific publications:
https://www.ncbi.nlm.nih.gov/pubmed/?term=Grünewald+TG
Pre-print publications:
https://www.biorxiv.org/search/author1%3AThomas%2BGrunewald%2B%20numresults%3A10%20sort%3Apublication-date%20direction%3Adescending%20format_result%3Astandard)
Endrit Vinca receives a Heinrich F. C. Behr scholarship from the DKFZ and Medical Faculty of the University of Heidelberg.
