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Cell Death and Childhood Cancers

Objectives

Despite decades of research and the implementation of several clinical trials, pediatric cancer survival rate has come to a standstill and 2/3 of cured children will experience life-threatening conditions throughout their life. Treatment upgrades for childhood cancers mainly rely on the transposition of adult data. However, children are anything but “small” adults and the types of cancers they develop are in most cases different from those of adults.
They appear in a singular developmental context of actively growing tissues, are not strongly linked to lifestyle, and display a lower overall mutational burden. Thus, to overcome resistance and prevent sequelae, we need to unravel the molecular and cellular underpinnings and specificities driving childhood cancers.
But, cancer in children is 40 times less frequent than adult cancers, with an incidence of ~1 in 7,000 children diagnosed each year. Therefore, one of the major challenges of pediatric cancer research is t the small size of the diseased population, and thus of the specimens available for research purposes.

Projects

The team “Cell Death and Childhood Cancers” was initiated in September 2016, around M. Castets, who has a robust expertise in basic research, notably on mechanisms triggering resistance of tumor cells to cell death and J.-Y. Blay, expert in translational and clinical research on sarcoma and rare cancers. The scientific projects are interconnected; they are supervised and coordinated by M. Castets, A. Dutour, L. Broutier, M. Billaud and M. Cordier-Bussat, and J.-Y. Blay who have specific complementary skills. Moreover, the projects are intricately linked to clinical aspects owing to the close interaction with the clinicians of the team, Dr. N. Corradini and Dr. P. Leblond experts in sarcomas and brain tumors of children and adolescents/young adults (AJA), respectively.

Resistance to cell death plays a key role in the first pathological steps towards cancer as well as in constitutive or acquired resistance to treatments. Based on the assumption that children are anything but little adults, our main objective is to elucidate childhood cancers resistance to cell death mechanisms, focusing on their developmental origin context and intratumoral heterogeneity, to move towards more efficient and less toxic innovative therapeutic strategies. More precisely, our research aims at:

  • Developing childhood and AYA innovative models
  • Unravelling the developmental processes hijacked by tumor cells to survive (Dr. M.Castets)
  • Addressing the role of intratumoral heterogeneity & dynamics in resistance to cell death (Dr. L. Broutier)
  • Triggering tumor cells elimination, notably via immune system stimulation. (Dr. A. Dutour) or by metabolic targeting (Dr. M. Cordier-Bussat and Dr. M. Billaud)

The C3 team also coordinates the Share4kids project, supported by the INCa, aiming at creating a multi-omics data warehouse in pediatric oncology available to all researchers. This is part of the React4kids network.

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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