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Cell States and Childhood Cancers

Objectives

Pediatric and young adult cancers represent a major scientific and medical challenge. Unlike adult cancers, they arise in rapidly developing tissues and display distinct molecular signatures dominated by epigenetic alterations. This biological specificity requires dedicated research approaches to understand their mechanisms and develop adapted therapies.
The past decade has transformed our ability to analyze these tumors, notably through multi-omic sequencing and the development of innovative experimental models. Our team has embraced this dynamic by developing organoid models of pediatric sarcomas and gliomas and bioinformatics expertise to analyze tumor cell plasticity.
Our central hypothesis is that quiescent and invasive cell states represent the most aggressive phenotypes in rhabdomyosarcomas and high-grade gliomas. Our objective is therefore to decipher the dynamics of these cell states and identify the molecular mechanisms governing their emergence and maintenance, to develop targeted therapeutic strategies.

 

Graphical Abstract – Decoding and Targeting Aggressive Cell States in Pediatric and Youth Cancers: A Tumoroid-Based Multi-Omics Approach for Precision Therapy

Projects

To carry out this project, our team brings together clinicians specializing in sarcomas and brain tumors (N. Corradini, P. Leblond, A. Bertrand), cancer biology researchers (M. Castets, A. Dutour, L. Broutier, M. Cordier-Bussat, A. Hennino), and bioinformaticians, under the co-leadership of Marie Castets and Jean-Yves Blay. We work on pediatric rhabdomyosarcomas and high-grade gliomas along three complementary axes:
1. Tracking tumor cell evolution We follow tumor cells through time and space using our organoid models. By combining multi-omic analyses and 3D imaging, we observe how cells change state – transitioning from proliferative to quiescent or invasive – in response to treatments or their environment. This dynamic mapping reveals key moments for therapeutic intervention.
2. Identifying resistance mechanisms We decipher the “molecular switches” that enable cells to become aggressive. Our recent work has shown that developmental pathways like BMP are hijacked to confer invasive properties. By modulating these pathways through genetic editing or pharmacological approaches, we validate their role in therapeutic resistance.
3. Designing innovative therapies By exploiting specific vulnerabilities of each cell state, we develop rational therapeutic combinations. Our mathematical models optimize treatment regimens to eliminate all tumor populations. Promising compounds, including our patented mitoselectins, are tested on organoids then validated in vivo before clinical translation.
Serving the community:
  • Leading Share4Kids: National platform gathering multi-omic data from hundreds of pediatric tumors, accessible to all researchers via a user-friendly interface developed with ADLIN-Science (€1M, INCa/MSD-AVENIR)
  • Coordinating React4Kids network: 600+ researchers with training, doctoral collaborations, and annual conferences
  • SouthROCK: INCa-certified Lyon-Marseille excellence center in pediatric oncology
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Members

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Fundings

  • Ligue Nationale Contre le Cancer – AAP Enfants, Adolescents et Cancer
  • INCA – PediaMod 2022
  • INCA – HRHG 2020
  • PEDIAC
  • Robert J. Arceci Innovation Award
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Publications