Imipridones ONC201/ONC206 + RT/TMZ triple (IRT) therapy reduces intracranial tumor burden, prolongs survival in orthotopic IDH-WT GBM mouse model, and suppresses MGMT (IMAGE)
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Figure 1: ONC201 synergizes with RT. (A) Combination of ONC201 and RT treated GBM cell lines SNB19, T98G, and U251, and atypical teratoid rhabdoid tumor (ATRT: BT-12, BT-16) cell lines show treatment effects on cell viability. (B) Colony formation assays with ONC201 up to 4 μM alone or in combination with radiotherapy up to 8 Gy. Blue boxes are dose combinations that show synergy between ONC201 and radiation therapy. Combenefit was used to evaluate the interaction of multiple treatments on short term cell viability and long-term colony formation assay - synergistic combinations are denoted by a synergy score greater than zero. (C) Western blots were utilized to assess induction of PKA substrate phosphorylation, induction of ATF4 as a marker of ISR activation, and multiple markers of cell death such as cleaved PARP and cleaved Caspase 3 in treated brain tumor cells.
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