EXTH-90. HDAC INHIBITOR, CAY10603, IS A POTENT RADIOSENSITIZER IN MENINGIOMAS

Abstract Developing and evaluating potential radiosensitisers to enhance therapeutic efficacy are urgently needed due the lack of efficient chemotherapy for meningioma. Histone deacetylase (HDACs) expression is generally increased in many cancer types regulate numerous proteins involved tumorigenesis. Targeting HDAC using inhibitor (HDACi) represent promising that affect various biological processes, such as cell survival, apoptosis, DNA repair. Recently, one inhibitor, AR42 monotherapy trials patients with neurofibromatosis type2 started Nov 2021. However, we were not able detect actual downregulation after applying (0.5-2 μM) immortalised Hence, investigated whether pretreatment hydroxamate-based HDAC6 Cay10603, impacts expression, radiation-induced double-strand break (DSB) induction, cycle arrest both human meningioma lines. Cay10603 at nanomolar level (100 nM) was treated prior high energy x-ray irradiation (2 Gy) by a medical linear accelerator (LINAC). We found surviving rate synergistically decreased combination treatment radiation. Combination therapy induced damage activation histone gH2AX G2/M compared drug or radiation alone. To focus on mechanisms action inhibition followed radiation, further nuclear localisation beta-catenin levels. The results showed nucleus suppressed therapy. Our findings demonstrate strategy improve radiosensitization meningiomas.