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PREDICT SIGNED

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

Total Cost €

EC-Contrib. €

Partnership

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PREDICT project word cloud

Explore the words cloud of the PREDICT project. It provides you a very rough idea of what is the project "PREDICT" about.

always complexity properly setting xenograft nude activated model repository almost subsequent genetic thereby medicine prevented global treatment phase1 alternative profile efficient synergistic generate evolution effective purpose ongoing optimal validation chemotherapy benefit tested options assigning models focusses predict vivo prognosis select complete single shows therapy identification organoids mice individual heterogeneity programs trials molecular combinations clinical poor precision simultaneous patients neuroblastoma vitro human subtypes intervention relapse combination aberrations personalized pipeline pediatric organoid tumor compound perform tumors compounds remission small difficult mimic poorly

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 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.	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

List of publications.
year	authors and title	journal	last update
2019	David T. W. Jones, Ana Banito, Thomas G. P. GrÃ¼newald, Michelle Haber, Natalie JÃ¤ger, 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. GrÃ¶bner, 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 HÃ¼bschmann, Gideon Zipprich, Michael Heinold, JÃ¼rgen 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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