Inhibition of DHFR targets the self-renewing potential of brain tumor initiating cells

Brain tumors are a heterogeneous group of benign and malignant arising from the brain parenchyma its surrounding structures, with in general poor clinical outcome due to high recurrence. One underlying causes for this somber prognostic is presence tumor initiating cells (BTIC) endowed self-renewal potential, multi-lineage differentiation resistance treatment. promising therapeutic avenue targeting BTIC potential forcing their differentiation. A compelling candidate one-carbon metabolism shown play key role maintaining stem cell several lineages. Here, we focus on dihydrofolate reductase (DHFR), enzyme metabolism, demonstrate enzyme's overexpression human expression BTIC. We show that DHFR inhibition, either by Methotrexate (MTX) or EphB activation synthetic ligands, reduces tumorigenic 4 lines, reducing capacities both vitro cerebral organoid glioma (GLICO) model. Our data indicate driving inhibiting may provide new approach treating highly refractory aggressive tumors.