More on ONC201

ONC201 also demonstrates synergistic effects with other cancer therapeutics to induce apoptosis in various types of cancers. In a study of glioblastoma, ONC201 synergized with ABT263 (Navitoclax), a small molecule inhibitor of the Bcl-2 protein family and BH3-mimetic, to induce apoptosis. Reduction of tumors were observed in vivo without any adverse side effects or toxicity (Karpel-Massler et al. 2015). In another study involving pancreatic adenocarcinoma, ONC201 activated both extrinsic (TRAIL-caspase-8-dependent) and intrinsic (caspase-9-dependent) apoptosis pathways while synergizing with gemcitabine, a common chemotherapy for this cancer, to inhibit Panc-1 xenograft growth in mice (Zhang et al. 2016). This combination therapy also increased the mice’s survivability.