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SARCOMAkids

Financiado

Developmentally programmed pediatric sarcomas: a versatile platform for drug dis...

Developmentally programmed pediatric sarcomas: a versatile platform for drug discovery and molecular precision medicine Pediatric sarcomas account for ~20% of childhood cancers. They have disappointing survival rates, with very little therapeutic progress over the last three decades. We clearly have to rethink the science and find new ways to tackl... ver más

30/09/2028

ST. ANNA KINDERKRE...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

ST. ANNA KINDERKREBSFORSCHUNG GMBH No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-09-25

ERC-2022-COG: ERC CONSOLIDATOR GRANTS Scope:Objectives

I+D

Cerrada hace 2 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

ST. ANNA KINDERKREBSFORSCHUN...

2.00M€ | Lider

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Duración del proyecto: 60 meses Fecha Inicio: 2023-09-25
Fecha Fin: 2028-09-30

Líder del proyecto

ST. ANNA KINDERKREBSFORSCHUNG GMBH No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Pediatric sarcomas account for ~20% of childhood cancers. They have disappointing survival rates, with very little therapeutic progress over the last three decades. We clearly have to rethink the science and find new ways to tackle these devastating tumors. I propose that new cellular models are needed that account for the developmental origins of pediatric sarcoma, in order to accelerate drug discovery and molecular precision medicine. Focusing on Ewing sarcoma, which is a developmental cancer caused by a (known) fusion oncogene expressed in (unknown) cells-of-origin, we will pursue a build it to understand it approach and construct in vitro and in vivo tumor models starting from human pluripotent stem cells (hPSCs). We will validate these models against our single-cell and spatial maps of Ewing sarcoma tumors, and we will pursue initial applications in academic drug discovery – targeting the regulatory programs of Ewing sarcoma cells, metabolic dependencies of the tumor microenvironment and developmentally programmed tumors in their in vivo context. To build Ewing sarcoma models in a molecular defined manner, we will map oncogene-competent cell states by inducing EWS-FLI1 expression in hPSC-based models of human development (Aim 1). We will create supportive tumor microenvironments by 3D differentiation and CRISPR screening in stromal cells (Aim 2). Finally, we will evaluate the ability of in vitro models to form tumors in mice, and we will pursue full in vivo modeling of Ewing sarcoma using genetically engineered teratomas (Aim 3). Compared to patient-derived xenografts, organoids or cell lines, our approach captures early events of tumorigenesis, providing complementary in vitro and in vivo models of Ewing sarcoma for biomedical and translational research. This approach will generalize to other tumor types, as it takes the concept of developmental cancers seriously and operationalizes it using cellular programming and high-throughput functional biology.

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