U1360 - Oncogenesis, Resistance, and Therapeutic Targets in Pediatric Cancers

Themes, Objectives, and Challenges

The unit is developing an integrated approach focused on aggressive pediatric cancers, including acute myeloid leukemia (AML), diffuse midline gliomas (DMG/DIPG), and metastatic osteosarcomas. The goal is to identify the molecular, cellular, and developmental mechanisms underlying these cancers and their resistance in order to design more effective and less toxic therapeutic strategies. Our research draws on large clinical cohorts and cutting-edge technologies: multi-omic and single-cell analyses, CRISPR-Cas9 functional screens, syngeneic or patient-derived (PDX) models, induced pluripotent stem cells (iPSCs), and organoids. The unit has created a unique multidisciplinary environment bringing together researchers, physicians, and pharmacists in close collaboration with leading national and international programs in pediatric oncology.

Results, Prospects, and Scientific, Clinical, and Societal Impacts

The unit’s work aims to make fundamental discoveries in pediatric oncology and accelerate their translation to patients through close integration with clinical trials. Longitudinal analysis of tumor samples and circulating tumor DNA will enable the identification of new diagnostic or theranostic biomarkers, as well as mechanisms of treatment resistance, in order to propose innovative therapeutic approaches and combinations. The unit already contributes to several research networks (e.g., PEDIAC, Paris Kids Cancer, ITCC), includes physicians leading international clinical trials (e.g., AcSé-ESMART, BIOMEDE, FOSTER, SACHA), and collaborates with patient organizations, startups, and industry partners to foster biomedical innovation. Ultimately, this research aims to improve survival rates for children and adolescents with aggressive cancers and reduce the long-term side effects of treatment.