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PREDICT SIGNED

PREcision medicine Drug combination testing In neuroblastoma organoids to guide Clinical Trials

Total Cost €

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EC-Contrib. €

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Partnership

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Project "PREDICT" data sheet

The following table provides information about the project.

Coordinator
PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE BV 

Organization address
address: HEIDELBERGLAAN 25
city: UTRECHT
postcode: 3584CS
website: www.prinsesmaximacentrum.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Total cost 1˙406˙250 €
 EC max contribution 1˙406˙250 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-STG
 Funding Scheme ERC-STG
 Starting year 2017
 Duration (year-month-day) from 2017-03-01   to  2022-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    PRINSES MAXIMA CENTRUM VOOR KINDERONCOLOGIE BV NL (UTRECHT) coordinator 1˙406˙250.00

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 Project objective

Neuroblastoma are pediatric tumors that respond poorly to chemotherapy and have a very poor prognosis. To improve treatment options, a global development towards precision medicine is ongoing. This strongly focusses on molecular genetic target identification in tumors and subsequent assigning patients to the best trials according to their molecular profile. Still it is difficult to predict which patients will benefit from these targeted compounds. In addition, if tumors do respond to single compound targeted therapy, they almost always relapse. These tumor evolution processes could be prevented by simultaneous intervention in different activated tumor pathways.

We now want to study how we can select patients that will most likely respond to a targeted compound and what combinations of targeted compounds are most effective? This can’t be tested in a clinical setting since the number of neuroblastoma patients that can be included in Phase1/2 trials is very small. Recent research shows that tumor organoids mimic human tumors and can effectively be used as xenograft in nude mice as well. These in vitro and in vivo models could be used as an alternative selection system for optimal combination treatment in a personalized approach.

The overall aim is now to test if combinations of targeted compounds can cause complete remission in neuroblastoma organoid model systems to select combination treatment options for personalized clinical trials

For this purpose we will generate neuroblastoma organoids that properly represents the complexity and heterogeneity of individual tumors and build a repository that represents the various subtypes of neuroblastoma tumors. We will identify synergistic compound combinations that are effective in neuroblastoma tumors that are characterized by specific molecular genetic aberrations. Thereby we will build an efficient pipeline to generate personalized models that can be used in precision medicine programs to perform compound validation.

 Publications

year authors and title journal last update
List of publications.
2019 David T. W. Jones, Ana Banito, Thomas G. P. Grünewald, Michelle Haber, Natalie Jäger, Marcel Kool, Till Milde, Jan J. Molenaar, Arash Nabbi, Trevor J. Pugh, Gudrun Schleiermacher, Malcolm A. Smith, Frank Westermann, Stefan M. Pfister
Molecular characteristics and therapeutic vulnerabilities across paediatric solid tumours
published pages: 420-438, ISSN: 1474-175X, DOI: 10.1038/s41568-019-0169-x
Nature Reviews Cancer 19/8 2020-02-13
2018 Susanne N. Gröbner, Barbara C. Worst, Joachim Weischenfeldt, Ivo Buchhalter, Kortine Kleinheinz, Vasilisa A. Rudneva, Pascal D. Johann, Gnana Prakash Balasubramanian, Maia Segura-Wang, Sebastian Brabetz, Sebastian Bender, Barbara Hutter, Dominik Sturm, Elke Pfaff, Daniel Hübschmann, Gideon Zipprich, Michael Heinold, Jürgen Eils, Christian Lawerenz, Serap Erkek, Sander Lambo, Sebastian Waszak, C
The landscape of genomic alterations across childhood cancers
published pages: 321-327, ISSN: 0028-0836, DOI: 10.1038/nature25480
Nature 555/7696 2020-02-13

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