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Restoration of tumor suppressor function by induction of translational read thro...

Restoration of tumor suppressor function by induction of translational read through of premature termination codons a strategy for improved cancer therapy 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 termina... see more

28/02/2022

2M€

Project Budget: 2M€

Project leader

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

PARTICIPATION DEPralty Sin fecha límite de participación.

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Financing granted El organismo H2020 notifico la concesión del proyecto The day 2022-02-28

ERC-ADG-2015: ERC Advanced Grant Scope:Objectives

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Cerrada does 10 years

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Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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2 Participantes

2.48M€ | Leader

INTERNATIONAL CAPACITORS

700.10K€ | participant

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Project duration: 65 months Date Start: 2016-08-30
End date: 2022-02-28

Project leader

KAROLINSKA INSTITUTET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Project Budget 2M€

participation deadline Sin fecha límite de participación.

Project description 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.

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