LAUSR

Background: Glioblastoma multiforme (GBM) is the most common form of malignant brain tumor in adults. The prognosis of GBM is still poor despite first-line therapy, and the median overall survival (OS) is 12-15 months, while the 5-year survival does not exceed 5%. Despite aggressive initial treatment, most patients develop recurrent diseases. Novel drug combinations for malignant CNS tumors are under investigation. Panobinostat is a histone deacetylase inhibitor (HDACi) with antineoplastic and antiangiogenic effects in glioma, and we previously noted synergy with combination of panobinostat and imipridone ONC206. ONC206 is under clinical investigation for treating adult and pediatric brain tumor patients. We decided to investigate the triple combination of ONC206, Panobinostat and radiation against glioma cells. Materials & Methods: We investigated cell viability and drug synergies of ONC206 plus Panobinostat with or without radiation in 4 human GBM cell lines at 72 hours. Results: We identified synergy between impridone ONC206 and Panobinostat which improved with radiation therapy IC50 values of panobinostat and ONC206 against cell lines U138, U87, T98G & U251MG ranges from 29-85 nM & 0.8-1.2 μM, respectively. Synergies between ONC206 and Panobinostat were observed across cell lines with combination indices of <0.5 indicating strong synergy. When treating with 4GY radiation after 48 h, combination index improved. documenting enhanced tumor cell killing of human glioma cells. Conclusion: Our ongoing studies reveal synergy between ONC206, Panobinostat and radiation against GBM cell lines. The enhanced synergy with radiation provides an opportunity to develop a novel treatment combination for high grade glioma with a focus on recurrent GBM. Citation Format: Vida Tajiknia, Wafik El Deiry, Lanlan Zhou. Enhanced efficacy of HDAC inhibitor panobinostat and ONC206 combined with radiation therapy against human glioblastoma cell lines without H3K27M mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2831.