Description du projet
Caractérisation moléculaire des tumeurs cérébrales
Les tumeurs cérébrales sont hétérogènes et, contrairement aux malignités hématopoïétiques, la cellule d’origine est inconnue dans la plupart des cas. BRAIN-MATCH, une initiative financée par l’UE, entend comprendre la biologie des tumeurs cérébrales en analysant les profils moléculaires de cellules cérébrales normales à différents stades du développement, à une résolution unicellulaire, et en intégrant des milliers de jeux de données de tumeurs cérébrales couvrant plus de 100 entités tumorales différentes. Cette approche intégrative aidera les scientifiques à identifier les cellules à l’origine de nombre de ces tumeurs. Les résultats du projet impliquent également des projections cliniques et sont susceptibles de dévoiler des thérapies innovantes et des tests liquides basés sur la biopsie pour la détection des cellules tumorales circulant dans le sang.
Objectif
Brain tumors represent an extremely heterogeneous group of more than 100 different molecularly distinct diseases, many of which are still almost uniformly lethal despite five decades of clinical trials. In contrast to hematologic malignancies and carcinomas, the cell-of-origin for the vast majority of these entities is unknown. This knowledge gap currently precludes a comprehensive understanding of tumor biology and also limits translational exploitation (e.g. utilizing lineage targets for novel therapies and circulating brain tumor cells for liquid biopsies).
The BRAIN-MATCH project represents an ambitious program to address this challenge and unmet medical need by taking an approach that (i) extensively utilizes existing molecular profiles of more than 30,000 brain tumor samples covering more than 100 different entities, publicly available single-cell sequencing data of normal brain regions, and bulk normal tissue data at different times of development across different species; (ii) generates unprecedented maps of normal human CNS development by using state-of-the art novel technologies; (iii) matches these molecular portraits of normal cell types with tumor datasets in order to identify specific cell-of-origin populations for individual tumor entities; and (iv) validates the most promising cell-of-origin populations and tumor-specific lineage and/or surface markers in vivo.
The expected outputs of BRAIN-MATCH are four-fold: (i) delivery of an unprecedented atlas of human normal CNS development, which will also be of great relevance for diverse fields other than cancer; (ii) functional validation of at least three lineage targets; (iii) isolation and molecular characterization of circulating brain tumor cells from patients´ blood for at least five tumor entities; and (iv) generation of at least three novel mouse models of brain tumor entities for which currently no faithful models exist.
Champ scientifique
Mots‑clés
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
69120 Heidelberg
Allemagne