European Commission logo
français français
CORDIS - Résultats de la recherche de l’UE
CORDIS

Tumor cell death supports recurrence of cancer

Description du projet

Une thérapie anticancéreuse pourrait-elle aider les cellules tumorales à survivre?

La chimiothérapie a été conçue pour tuer les cellules cancéreuses et induire une régression de la tumeur. Des données suggèrent toutefois qu’elle pourrait involontairement favoriser la survie et la migration des cellules cancéreuses restantes vers des sites distants. Financé par le Conseil européen de la recherche, le projet Cancer-Recurrence entend identifier les mécanismes clés qui régissent la migration et la croissance des cellules tumorales survivantes après l’induction de la mort cellulaire. Les chercheurs caractériseront, par une approche pluridisciplinaire, les effets des cellules mourantes sur les cellules tumorales et stromales environnantes et identifieront des cibles potentielles pour atténuer les effets secondaires involontaires de la mort des cellules tumorales. Les connaissances acquises dans le cadre de cette recherche devraient contribuer au développement de nouveaux traitements anticancéreux plus efficaces.

Objectif

Introduction: Current anti-cancer treatments are often inefficient, while many patients initially benefit from anti-cancer drugs eventually experience relapse of resistant tumors throughout the body. Current clinical strategies mainly aim at inducing tumor cell death, but this induction may have unintentional and unwanted side effects on surviving tumor cells.

Preliminary data: We show that after chemotherapy-induced initial regression, PyMT mammary tumors reappear. During regression, we observe an increased number of cells that have undergone epithelial-mesenchymal transition (EMT) and become migratory. We show that migration can be induced upon uptake of extracellular vesicles (e.g. apoptotic bodies). Our findings suggest that EMT is induced upon chemotherapy, through e.g. EV uptake, potentially leading to migration and growth of surviving cells.

Hypothesis and main aim: Based on preliminary data, we hypothesize that tumor cell death induces migration and growth of the surviving tumor cells. We aim to identify the key cell types and mechanisms that mediate this effect, and establish whether interference with these cells and mechanisms can reduce recurrence of tumors after chemotherapy.

Approach: We have developed unique intravital imaging tools and genetically engineered fluorescent mice to visualize and characterize if and how dying tumor cells can affect surrounding surviving tumor and stromal cells. We will test whether dying tumor cells can influence the growth, migration, dissemination and metastasis of surviving tumor cells directly or indirectly through stromal cells. We will identify potential targets to block the influence of the dying tumor cells, and test whether this blockade inhibits the unintended side-effects of tumor cell death.

Conclusion: With the studies proposed in this grant, we will gain fundamental insights on how induction of tumor cell death, the universal aim of therapy, could play a role in growth and spread of surviving tumor cells.

Régime de financement

ERC-COG - Consolidator Grant

Institution d’accueil

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS
Contribution nette de l'UE
€ 1 564 393,60
Adresse
PLESMANLAAN 121
1066 CX Amsterdam
Pays-Bas

Voir sur la carte

Région
West-Nederland Noord-Holland Groot-Amsterdam
Type d’activité
Research Organisations
Liens
Coût total
€ 1 564 393,60

Bénéficiaires (2)