Medulloblastoma (MB) is the most common malignant brain tumor in children and presents a varied
prognosis, with some patients succumbing to the disease and survivors presenting neurotoxic sequelae
from treatment. Reprogramming of cellular metabolism is one of the hallmarks of cancer, therefore, in
the current study we focussed ...»»»»
Medulloblastoma (MB) is the most common malignant brain tumor in children and presents a varied
prognosis, with some patients succumbing to the disease and survivors presenting neurotoxic sequelae
from treatment. Reprogramming of cellular metabolism is one of the hallmarks of cancer, therefore, in
the current study we focussed on investigating the lipidomic profile of MB to identify novel therapeutic
strategies. We identified an increase of unsaturated fatty acids in MB compared to human neural stem
cells, that resulted in the identification of Stearoyl-CoA desaturase 1 (SCD1) as a potential therapeutic
target in MB. RNA sequencing of cells treated with SCD1 inhibitor resulted in the activation of several
interconnected pathways that regulate apoptosis, proliferation, differentiation, inflammation, and
metabolic homeostasis. Moreover, microarray expression data from a cohort of 763 pediatric MB patient
samples was investigated, identifying that SCD expression is a prognostic marker in Group 3 and Group
4 MB subgroups. In addition, we identified that Group 3 and Group 4 MB patient samples with very high
SCD expression may be enriched in cholesterol homeostasis and specific amino acid metabolic pathways
(glycerine, serine, and threonine), while those with very low SCD expression were enriched in purine
nucleotide metabolism. Finally, we propose potential combinatorial or synergistic therapies with SCD1
inhibition to avoid potential resistance, including the use of beta-blockers, NF-KB inhibitors, or statins.^^^^
