biostudies-literatureThang MEshelman Institute for Innovation, University of North Carolina at Chapel HillNCATSNCATS NIH HHSNational Cancer InstituteNCI NIH HHSNational Institutes of HealthUniversity of North Carolina at Chapel Hill200834https://www.ebi.ac.uk/biostudies/studies/S-EPMC11263637biostudies-literatureUnknown32(3)Tumor-homing neural stem cell (NSC) therapy is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tumor-homing NSC therapy therapies that maintain durable tumor suppression remains a challenge. Herein, we report a synergistic combination regimen where the novel small molecule TR-107 augments NSC-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy (hiNeuroS-TRAIL) in models of the incurable brain cancer glioblastoma (GBM) <i>in vitro</i>. We report that the combination of hiNeuroS-TRAIL and TR-107 synergistically upregulated caspase markers and restored sensitivity to the intrinsic apoptotic pathway by significantly downregulating inhibitory pathways associated with chemoresistance and radioresistance in the TRAIL-resMolecular therapy. OncologyCombining the constitutive TRAIL-secreting induced neural stem cell therapy with the novel anti-cancer drug TR-107 in glioblastoma.PMC11263637U01 TR003715F30CA243270T32 CA071341Kass LEHingtgen SDDaglish SFennell EMJMann BEMellows CMercer-Smith ARValdivia AThang MGraves LMfalseCombining the constitutive TRAIL-secreting induced neural stem cell therapy with the novel anti-cancer drug TR-107 in glioblastoma.Tumor-homing neural stem cell (NSC) therapy is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tumor-homing NSC therapy therapies that maintain durable tumor suppression remains a challenge. Herein, we report a synergistic combination regimen where the novel small molecule TR-107 augments NSC-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy (hiNeuroS-TRAIL) in models of the incurable brain cancer glioblastoma (GBM) <i>in vitro</i>. We report that the combination of hiNeuroS-TRAIL and TR-107 synergistically upregulated caspase markers and restored sensitivity to the intrinsic apoptotic pathway by significantly downregulating inhibitory pathways associated with chemoresistance and radioresistance in the TRAIL-res2024-01-01T00:00:00Z2024 Sep2026-06-01T20:38:32.262Z2025-06-01T01:16:09.665ZS-EPMC112636373904502910.1016/j.omton.2024.200834