Developmentally programmed pediatric sarcomas: a versatile platform for drug discovery and molecular precision medicine

Title	Developmentally programmed pediatric sarcomas: a versatile platform for drug discovery and molecular precision medicine
Acronym	SARCOMAkids
Website	https://ccri.at/research-group/eleni-tomazou-group/
Start date	2023-09-01
End date	2028-08-31
Sponsor	European Research Council - Consolidator Grant (ERC-CoG)
Institution	St. Anna Kinderkrebsforschung GmbH

Associated cell lines

• WAe001-A (H1, WA01)
• WAe007-A (H7, WA07)
• WAe009-A (H9, WA09)

Project Description

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 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).