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TRANSREAD SIGNED

Restoration of tumor suppressor function by induction of translational read-through of premature termination codons - a strategy for improved cancer therapy

Total Cost €

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EC-Contrib. €

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Partnership

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Project "TRANSREAD" data sheet

The following table provides information about the project.

Coordinator
KAROLINSKA INSTITUTET 

Organization address
address: Nobels Vag 5
city: STOCKHOLM
postcode: 17177
website: www.ki.se

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 Sweden [SE]
 Total cost 2˙480˙889 €
 EC max contribution 2˙480˙889 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KAROLINSKA INSTITUTET SE (STOCKHOLM) coordinator 2˙480˙889.00

Map

 Project objective

Tumor suppressor genes such as TP53, RB1, PTEN and APC are frequently inactivated in sporadic and inherited human tumors. A significant fraction of the mutations in these genes are nonsense mutations that lead to premature termination of translation and expression of truncated unstable and non-functional proteins. We will identify and characterize novel molecules that can induce translational read-through of premature termination codons in nonsense mutant TP53 and expression of full length p53 protein. Hits will be tested for their effect on nonsense mutant RB1, PTEN and APC. We will also elucidate the molecular mechanism of action of the identified compounds by CETSA and other techniques. Moreover, we will test hit compounds on primary tumor cells from patients ex vivo, and generate mouse knock-in tumor models with nonsense mutant tumor suppressor genes for further characterization of hits. We will take the most promising hits through preclinical development towards clinical trials. Our aim is to develop novel and efficient targeted therapy for tumors with nonsense mutations in the TP53, RB1, PTEN and/or APC tumor suppressor genes.

 Publications

year authors and title journal last update
List of publications.
2018 Meiqiongzi Zhang, Angelos Heldin, Mireia Palomar-Siles, Susanne Öhlin, Vladimir J. N. Bykov, Klas G. Wiman
Synergistic Rescue of Nonsense Mutant Tumor Suppressor p53 by Combination Treatment with Aminoglycosides and Mdm2 Inhibitors
published pages: , ISSN: 2234-943X, DOI: 10.3389/fonc.2017.00323
Frontiers in Oncology 7 2019-06-13

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