Descrizione del progetto
Caratterizzazione molecolare dei tumori al cervello
I tumori al cervello sono eterogenei e, a differenza delle neoplasie ematopoietiche, la cellula d’origine è ignota nella maggior parte dei casi. BRAIN MATCH, un’iniziativa finanziata dall’UE, si propone di comprendere la biologia dei tumori al cervello analizzando i profili molecolari delle cellule cerebrali normali in fasi differenti dello sviluppo con una risoluzione a singola cellula e integrando migliaia di set di dati sui tumori al cervello che riguardano più di 100 diverse entità di tumore al cervello. Questo approccio integrativo aiuterà gli scienziati a individuare le cellule d’origine di molti di questi tumori. I risultati del progetto offrono anche proiezioni cliniche e mirano a indicare nuove terapie ed esami basati su biopsie liquide per l’individuazione di cellule tumorali che circolano nel sangue.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
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Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
69120 Heidelberg
Germania