CONTACT

·         Co-directors

Jean-Yves BLAY, PU-PH CLB/UCBL
jean-yves.blay@lyon.unicancer.fr

Marie CASTETS, CRCN Inserm
marie.castets@lyon.unicancer.fr

·         Principal investigators

Aurélie DUTOUR, CLB Researcher
aurelie.dutour@lyon.unicancer.fr

Laura BROUTIER, CRCN INSERM
laura.broutier@lyon.unicancer.fr

·         Clinicians

Nadège CORRADINI, PH, MD-PhD
Nadege.CORRADINI@ihope.fr

Pierre LEBLOND, PH, MDPhD
pierre.leblond@ihope.fr

·         Post-doctorant researchers

Kathrin WEBER, PhD
Katrin.WEBER@lyon.unicancer.fr

·         PhD students

Marie-Anaïs LOCQUET
MarieAnais.LOCQUET@lyon.unicancer.fr

Alejandro LOPEZ-GONZALES
alejandro.lopezgp@gmail.com

Joseph BISACCIA
Joseph.BISACCIA@lyon.unicancer.fr

Arthur TOURBEZ
Joseph.BISACCIA@lyon.unicancer.fr

Paul HUCHEDE
Paul.HUCHEDE@lyon.unicancer.fr

·         Engineers, technicians

Nina MEYNARD, IE
Nina.MEYNARD@lyon.unicancer.fr

Virginie BARBET, IE
Virginie.BARBET@lyon.unicancer.fr

Juliette GEOFFRAY, IE
Juliette.GEOFFRAY@lyon.unicancer.fr

Séverine FAGAULT, AI
Severine.FAGAULT@lyon.unicancer.fr

Voir les objectifs et projets Voir les publications

MEDICAL & SCIENTIFIC CONTEXT

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.

C3 TEAM 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. Scientific projects are supervised by M. Castets, A. Dutour, L. Broutier and J.-Y. Blay who have specific but complementary competences. This team organization is a key issue to develop an innovative and challenging research program on rare cancers, that will further our knowledge on basic sciences to move towards new therapeutic strategies.

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)

PUBLICATIONS

  • Locquet MA, Ichim G, Bisaccia J, Dutour A, Lebecque S, Castets M* and Weber K*. Caspase-8 deficiency induces a switch from TLR3-induced apoptosis to lysosomal cell death in neuroblastoma cell lines. In revision.

  • Vial J, Basset F*, Fagault S*, Creveaux M, Neves D, Rieusset J, Fauvelle F, Sujobert P, Dutour A, Blay JY, Weber K, Castets M, Loss of ANT1 confers a selective advantage to rhabdomyosarcoma tumor cells. In revision.

  • Monchanin M, Richert I, Simard F, Berchard B, Langlois JB, Vienne M, Bernet A, Gadot G, Blay JY, Dutour A, Anti Netrin 1 Ab exerts antitumor activity in combination with doxorubicin and modulates tumor immune environment in osteosarcoma models. In preparation.

  • Combaret V, Iacono I, Bellini A, Brejon S, Bernard V, Marabelle A, Coze C, Pierron G, Lapouble E, Schleiermacher G, Blay JY, Detection of tumor ALK status in neuroblastoma patients using peripheral blood. Cancer medicine. 2015;4:540-550.

  • Broutier L, Andersson-Rolf A, Hindley CJ, Boj SF, Clevers H, Koo BK, Huch M, Culture and establishment of self-renewing human and mouse adult liver and pancreas 3D organoids and their genetic manipulation. Nature protocols. 2016;11(9):1724-43.

  • Broutier L, [...], Vial J, [...], Castets M, Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas. EMBO molecular medicine. 2016;8(2):96-104.

  • Broutier L, [...], Huch M, Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nature medicine. 2017;23(12):1424-35.

  • Vial J, [...], Castets M, The Ectodysplasin receptor EDAR acts as a tumor suppressor in melanoma by conditionally inducing cell death. Cell death and differentiation. 2019;26(3):443-54.
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