In this context, we believe that a more detailed knowledge of the mechanisms by which HIF-1α and Wnt signaling co-factors can regulate GBM cell phenotype would open the way to a drug-based interference of their molecular competitors/inhibitors, in order to promote GBM cell differentiation and sensitize them to treatments, with the final aim of improving patient survival. The gene discussed is HIF1A; the disease is glioblastoma.