Descripción del proyecto
Caracterización molecular de los tumores encefálicos
Los tumores encefálicos son heterogéneos y, al contrario de lo que sucede con las neoplasias hematopoyéticas malignas, en la mayoría de los casos, no se conoce el origen celular. La iniciativa financiada con fondos europeos BRAIN-MATCH tiene por objeto comprender la biología de los tumores encefálicos mediante el análisis a resolución celular de los perfiles moleculares de las células encefálicas normales en distintas fases del desarrollo, e integrando esta información con miles de conjuntos de datos de tumores encefálicos que abarcan más de cien entidades tumorales encefálicas diferentes. Este método integrador ayudará a los científicos a determinar las células que dan lugar a muchos de estos tumores. Los resultados del proyecto también permitirán realizar proyecciones clínicas y abrirán vías hacia el descubrimiento de nuevos tratamientos y ensayos basados en biopsia líquida para la detección de las células tumorales circulantes en la sangre.
Objetivo
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.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
69120 Heidelberg
Alemania