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Decode Relapse

Financiado

Decoding and Targeting Treatment-Resistant Metastatic Neuroblastoma

The childhood cancer neuroblastoma (NB) is a major challenge in pediatric oncology, and children with relapse have a very poor prognosis due to treatment-resistance at metastatic sites. There is an urgent need to better understand... ver más

31/05/2029

LUNDS UNIVERSITET

2M€

Presupuesto del proyecto: 2M€

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LUNDS UNIVERSITET No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 1 Participantes

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-12-15

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

ERC-2023-COG: ERC CONSOLIDATOR GRANTS

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Cerrada hace 1 año

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1 Participantes

LUNDS UNIVERSITET

2.00M€ | Lider

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Duración del proyecto: 65 meses Fecha Inicio: 2023-12-15
Fecha Fin: 2029-05-31

Líder del proyecto

LUNDS UNIVERSITET

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto The childhood cancer neuroblastoma (NB) is a major challenge in pediatric oncology, and children with relapse have a very poor prognosis due to treatment-resistance at metastatic sites. There is an urgent need to better understand NB treatment resistance to inform the design of novel therapeutic strategies. However, current models do not mimic relapsed human NB in its most common metastatic niches in the bone and bone marrow. We recently developed advanced patient-derived and humanized NB in vivo models and 3D tumor organoid models which are excellent tools for preclinical drug testing. Here, we aim to further develop and exploit these models, investigate mechanisms of NB metastatic treatment resistance/relapse, and target relapsed NB with combination therapies. First, we will develop patient-derived in vivo and ex vivo models of relapsed NB in the human metastatic bone marrow niche exposed to standard-of-care chemotherapy treatment. These models will be exploited to investigate mechanisms of metastasis and treatment escape upon therapy and at relapse. We will integrate NB and stromal cell lineages, cell states and molecular details with phenotype and drug response, and elucidate NB tumor cell plasticity and clonal evolution. The mechanistic data and our new models will help us to identify novel therapeutic targets and compounds targeting relapsing and resistant NB, which we will validate experimentally. The project will lead to a deeper understanding of NB metastatic treatment resistance and identification of novel cell state-directed treatments to target resistant and metastatic disease. My combined background in clinical medicine/pathology, in vivo/ex vivo modeling, NB chemoresistance, and preclinical drug testing coupled with development and application of state-of the-art advanced assays will generate the next generation of patient-derived models, mechanistic insight and novel treatment against relapsed NB.

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