MGMT and glioblastoma: Based on the discovery of stimulatory synaptic connections between neurons and GBM mediated by monoamines and their receptors [34, 35], and on our previous work demonstrating the direct antitumor potential of CPZ and its synergistic effects with TMZ in restraining GBM growth in vitro [36], we carried out a Phase II multicenter clinical trial to evaluate the efficacy of CPZ in combination with TMZ in the first-line treatment of GBM patients with an unmethylated MGMT gene promoter, a group known to exhibit higher resistance to TMZ [37].