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TKI resistance

Financiado

Resistance mechanisms to tyrosine kinase inhibitors in solid tumors

Over the past 10 years, the chemotherapeutic arsenal has been expanded to include molecular-targeted therapies based on the principle that cancer cells become addicted to a single driver oncogene. However, use of these new therapi... ver más

30/11/2021

INSTITUT GUSTAVE R...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

INSTITUT GUSTAVE ROUSSY No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2021-11-30

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2016-STG: ERC Starting Grant

I+D

Cerrada hace 9 años

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2 Participantes

INSTITUT GUSTAVE ROUSSY

1.50M€ | Lider

RADIACION Y MICROONDAS

180.56K€ | Participante

Últimas noticias

25-11-2024: ECE En las últimas 48 horas el Organismo ECE ha otorgado 52 concesiones

25-11-2024: CMVAMADRID En las últimas 48 horas el Organismo CMVAMADRID ha otorgado 1 concesiones

25-11-2024: FUNDACION-EOI En las últimas 48 horas el Organismo FUNDACION EOI ha otorgado 6 concesiones

Duración del proyecto: 60 meses Fecha Inicio: 2016-11-28
Fecha Fin: 2021-11-30

Líder del proyecto

INSTITUT GUSTAVE ROUSSY

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Over the past 10 years, the chemotherapeutic arsenal has been expanded to include molecular-targeted therapies based on the principle that cancer cells become addicted to a single driver oncogene. However, use of these new therapies is limited due to development of acquired resistance. To fully understand how resistance develops, patient-derived models are an absolute pre-requisite, but establishing them remains extremely challenging. Few groups worldwide have successfully implemented a systematic standardized approach to facilitate translational cancer research discovery. My project aims to provide rational therapeutic guidance for combinatorial or adaptive designs to overcome acquired resistance to tyrosine kinase inhibitors (TKIs) in patients with oncogene-addiction. By establishing new laboratory models of resistance directly from patient biopsies (patient derived cell lines and xenografts) I will elucidate the molecular mechanisms whereby cancer cells escape targeted treatments. I will then implement innovative approaches to overcome resistance using TKI combinatorial screens, apoptosis sensitizers and by screening for epigenetic modifiers. Additionally, I will scrutinize the emergence of resistance acquisition in vitro. Current working models involve persistor cellular populations able to tolerate the TKI and, in a subsequent step, to become fully resistant to the drug. This drug tolerant persistor stage most probably involves epigenetic reprogrammation. An epigenetic inhibitor screen will be performed to identify agents able to interfere with the emergence of persistors and ultimately with the acquisition of TKI resistance. These results should provide an alternative strategy to validate innovative combinatorial drug strategies to avoid emergence of resistance in patients.

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