CONTACT

Co-directors

Marie Castets, CR1 Inserm, HDR
marie.castets@lyon.unicancer.fr

Jean-Yves Blay, PUPH, HDR
jean-yves.blay@lyon.unicancer.fr

Cheney A, 1er étage
Centre Léon Bérard

DUTOUR Aurélie
Cadre biologiste, HDR
aurelie.dutour@lyon.unicancer.fr
CORRADINI Nadège

Pédiatre oncologue, MD-PhD
nadege.corradini@lyon.unicancer.fr

BASSET Fanny
BERCHARD Paul
MONCHANIN Morgane
RICHERT Izeulys
VIAL Jonathan
LOPEZ Alejandro
YACOUB Karam
FAGAULT Séverine
LOCQUET Marie-Anaïs
BISACCIA Joseph
Stager
Voir les objectifs et projets Voir les publications

OBJECTIVES

Yearly childhood cancer mortality rates in France and worldwide approximate 500 and 80,000 cases, respectively. 50 years ago, pediatric cancer recovery rates did not exceed 25%. With the advent of chemotherapies, initially developed for adults but also effective for children, the picture is no longer as bleak. Indeed, we estimate that approximately three out of four children currently recover from their illness. However, these rates have not evolved drastically since the end of the 90s, and current intensive multimodal treatments cause deleterious side effects in 2/3 children, notably secondary tumors and chronic pathologies. Pediatric oncologists are committed to maintaining, as long as possible, the well-being of patients during their treatment. It is therefore primordial to better understand the etiology of pediatric cancers and to identify novel driver genes characterizing these patients. 

PROJECTS

Consistently, our ongoing research project aims at characterizing the mechanisms underlying resistance to tumor cell death, in particular apoptosis. Our approach is centered around two major axes:
1) to perform large scale studies to map cell death inhibiting events (focusing on apoptotic gene alterations) and 2) to characterize the putative causal role of the candidate genes identified and to determine their relevance as therapeutic targets.
These research axes are currently being applied to sarcoma that encompasses a variety of rare tumors, all of which develop in connective tissue (i.e. cells that support other cells/tissues throughout the body). Our team focuses on rhabdomyosarcoma and osteosarcoma, representing the most common types of soft tissue and bone sarcomas in children and teenagers, respectively. We initiated a research program, early 2016, combining transcriptomic analyses and functional siRNA screening, in order to obtain a dynamic and comprehensive map of apoptotic pathways and factors altered in these tumors. Results of these large scale analyses are being extrapolated and three candidate genes, specifically implicated in tumorigenesis, are being investigated to ascertain whether they constitute actionable molecular events enabling us to restore cell death in these tumors.
This approach is also being extended to other childhood cancers, in which the pediatric oncologists working at the Pediatric Hematology and Oncology Institute (IHOPe, Lyon) have an internationally recognized expertise, in particular neuroblastoma.

PUBLICATIONS

Royet A, Broutier L, Coissieux MM, Malleval C, Gadot N, Maillet D, Gratadou-Hupon L, Bernet A, Nony P, Treilleux I, Honnorat J, Liebl D, Pelletier L, Berger F, Meyronet D, Castets M*, Mehlen P*. Ephrin-B3 supports glioblastoma growth by inhibiting apoptosis induced by the dependence receptor EphA4. Oncotarget. 2017 Apr 4;8(14):23750-23759.

* : co-last authors

Simard FA, Richert I, Vandermoeten A, Decouvelaere AV, Michot JP, Caux C, Blay JY, Dutour A. Description of the immune microenvironment of chondrosarcoma and contribution to progression. Oncoimmunology. 2016 Dec 7;6(2):e1265716.

Broutier L, Creveaux M, Vial J, Tortereau A, Delcros JG, Chazot G, McCarron MJ, Léon S, Pangault C, Gadot N, Colombe A, Boulland ML, Blachier J, Marie JC, Traverse-Glehen A, Donzé O, Chassagne-Clément C, Salles G, Tarte K, Mehlen P, Castets M. Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle  cell lymphomas. EMBO Mol Med. 2016 Feb 1;8(2):96-104.

Dutour A, Josserand V, Jury D, Guillermet S, Decouvelaere AV, Chotel F, Pointecouteau T, Rizo P, Coll JL, Blay JY. Targeted imaging of α(v)β(3) expressing sarcoma tumor cells in vivo in pre-operative setting using near infrared: a potential tool to reduce incomplete surgical resection. Bone. 2014 May;62:71-8. 


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