Metabolic determinants of stemness in medulloblastoma

Abstract

Medulloblastomas (MBs) are the most prevalent brain tumours in children. They are classified as grade IV, the highest in malignancy, with about 30% metastatic tumours at the time of diagnosis. Cancer stem cells (CSCs) are a small subset of tumour cells that can initiate and support tumour growth. In MB, CSCs contribute to tumour initiation, metastasis, and therapy resistance. Metabolic differences among the different MB groups have started to emerge. Sonic hedgehog tumours show enriched lipid and nucleic acid metabolism pathways, whereas Group 3 MBs upregulate glycolysis, gluconeogenesis, glutamine anabolism, and glut athione-mediated anti-oxidant pathways. Such differences impact the clinical behaviour of MB tumours and can be exploited therapeutically. In this review, we summarise the existing knowledge about metabolic rewiring in MB, with a particular focus on MB-CSCs. Finally, we highlight some of the emerging metabolism-based therapeutic strategies for MB.

Angiogenesis and Lymphangiogenesis in Medulloblastoma Development

“…Metastasis is the major cause of mortality in children with MB, mainly because the primary tumor is surgically removed early in the treatment process and because metastases appear very early during the development of the pathology [24]. Among the molecular subgroups of MB, Group 3 tumors are associated with the poorest prognosis and exhibit the highest incidence of metastasis, both at initial diagnosis and recurrence.…”