Projektbeschreibung
Molekulare Charakterisierung von Hirntumoren
Hirntumoren sind heterogen und im Gegensatz zu hämatopoetischen Malignomen ist die ursprünglich befallene Zellart in den meisten Fällen unbekannt. BRAIN-MATCH, eine EU-finanzierte Initiative, will die Biologie von Hirntumoren besser verstehen. Dazu analysiert es molekulare Profile von normalen Hirnzellen in verschiedenen Entwicklungsphasen mit Einzelzell-Auflösung und integriert Tausende von Datensätzen über Hirntumoren, die mehr als 100 verschiedene Hirntumorentitäten abdecken. Mithilfe dieses integrativen Ansatzes werden die Forschenden die Ursprungszellen vieler der Tumoren identifizieren können. Die Projektergebnisse werden auch in die Praxis hineinwirken und sollen neue Therapien und Flüssigbiopsie-Assays zur Erkennung von im Blut zirkulierenden Tumorzellen anstoßen.
Ziel
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.
Wissenschaftliches Gebiet
Schlüsselbegriffe
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
69120 Heidelberg
Deutschland