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Senescence therapy for cancer

Systemic treatment of advanced cancers is hampered by the development of drug resistance. To prevent resistance, my laboratory has in the past used functional genetic screens to discover several synthetic lethal drug combination t... ver más

31/03/2024

NKI AVL

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

STICHTING HET NEDERLANDS KANKER INSTITUUTANTO... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

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Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2024-03-31

ERC-2017-ADG: ERC Advanced Grant Scope:Objectives

I+D

Cerrada hace 7 años

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

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2 Participantes

NKI AVL

2.48M€ | Lider

SOCAMEX, S.A.

701.20K€ | Participante

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Duración del proyecto: 68 meses Fecha Inicio: 2018-07-09
Fecha Fin: 2024-03-31

Líder del proyecto

STICHTING HET NEDERLANDS KANKER INSTITUUTANTO... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Systemic treatment of advanced cancers is hampered by the development of drug resistance. To prevent resistance, my laboratory has in the past used functional genetic screens to discover several synthetic lethal drug combination therapies, which has resulted in 8 clinical trials to date, including one global phase 3 study. In this program, I propose a new approach to the treatment of cancer, which is not based on combinations of drugs, but rather on the sequential treatment with drugs. In a first treatment step, cells will not only be induced to stop dividing, but they will at the same time acquire a major new vulnerability that is subsequently targeted with a second drug that selectively kills cells having the newly acquired vulnerability. To accomplish this, we will take advantage of recent observations that the cellular senescence response is not only a property of primary cells, but can also be triggered in advanced cancers. Such senescent cells have dramatic changes in gene expression, chromatin structure and metabolism that we will exploit for their selective eradication. Using chemical compound libraries and loss-of-function genetic screens in cancer cells harboring a reporter gene that is activated selectively in senescent cells, we will search for genes and compounds that induce senescence in cancer cells. This will lead to the identification of compounds and/or signaling pathways whose inhibition induces senescence in cancer cells. We will also use chemical compound screens to find tools to selectively kill senescent cancer cells. We will use the targets and compounds identified in this program to test the in vivo efficacy of this one-two punch consecutive therapy approach: the first to induce senescence in cancer cells, the subsequent therapy to eradicate the senescent cells. We present here preliminary data that the concept of sequential drug treatment can be effective, which serves as an important proof of concept for the strategy proposed here.

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