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Decrypting neuro-cancer crosstalk in pediatric cancers of the peripheral nervous system

Description du projet

Le lien entre l’activité neuronale et le neuroblastome

Les neurosciences du cancer expliquent les interactions entre les tumeurs et le système nerveux. Dans les gliomes de haut grade, en particulier chez les enfants, les tumeurs utilisent les réseaux neuronaux pour se développer et se propager plus efficacement. Notre compréhension de ces interactions dans le système nerveux périphérique (SNP) est toutefois limitée. Le neuroblastome (NB), un cancer pédiatrique mortel qui survient dans les ganglions sympathiques ou la glande surrénale, reste mal compris, notamment en ce qui concerne l’influence de l’activité neuronale sur sa croissance. Le projet CANEUTREAT, financé par le CER, vise à combler ce manque de connaissances. En créant des modèles qui reproduisent l’environnement embryonnaire du neuroblastome, le projet étudiera la relation entre l’activité neuronale et les caractéristiques de la tumeur. L’objectif consiste à identifier de nouvelles stratégies de traitement.

Objectif

Cancer neuroscience has emerged as a major axis of cancer biology, at the crossroad of two biological areas. Multi-layered dialogs between cancer and nervous contingents have started to be unravelled, with pivotal roles of the nervous system in tumor initiation, growth and invasion, in turn amplified by cancer-induced hijacking of nervous functions. Specifically, brain tumors were shown to be integrated in bona fide neuron-to-cancer synaptic networks but also to capture neural-activity dependent released factors that boost their tumor properties. In the last years, this completely rewired the view of high-grade gliomas, especially those arising in the pediatric population, suggesting specific vulnerabilities when neural networks are being shaped. The knowledge regarding neuro-cancer crosstalk in the peripheral nervous system (PNS) is far more fragmented, and is even obscure in malignancies arising within peripheral nervous tissues. Neuroblastoma (NB) is an emblematic, deadly, pediatric cancer of the PNS, with primary tumors that develop in sympathetic ganglia or in the adrenal gland. Despite its occurrence in sites of active central-to-PNS synaptic contacts, whether neural activity impacts on NB tumor features and metastatic progression is fully unknown. We have conceived a model of NB that reproduces the embryonic and nervous microenvironment in which it arises but also the sequence of its metastatic progression. Guided by preliminary data, the objective of the proposal is to decrypt the panel of neuro-cancer functional interplays in NB, at the anatomical, electrophysiological and molecular level. We will deploy multidisciplinary and cutting-edge approaches to provide a comprehensive and dynamic picture of neuro-NB dialogs, in relevant models for this pediatric cancer. Our underlying aims are to identify novel entry points for therapeutic strategies, and to define subtypes of NB that would benefit from neuro-related therapies.

Champ scientifique (EuroSciVoc)

CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN. Voir: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

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Régime de financement

HORIZON-ERC - HORIZON ERC Grants

Institution d’accueil

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Contribution nette de l'UE
€ 1 836 141,00
Coût total
€ 1 836 141,00

Bénéficiaires (1)