Abstract 3896: Pimavanserin suppresses the growth of medulloblastoma by inhibiting Lyn/STAT3/MBSC signaling axis

Abstract Medulloblastoma (MB) is one of the most frequently occurring malignant brain tumors in children, which accounts for 20% of all pediatric brain tumors and 40% of posterior fossa tumors. Despite advancements in the understanding of MB pathogenesis and identification of novel therapeutic targets, MB has emerged to be one of the most lethal pediatric diseases with peak incidences occurring in children aged between 5 and 7 years old. Numerous factors have been identified to hamper the management of several brain tumors including MB. However, the presence of medulloblastoma stem cells (MBSCs) and impermeability of drugs to cross the blood brain barrier (BBB) are identified as the major obstacles in MB management. MB is highly enriched with MBSCs, a subpopulation of MB cells that imparts therapy resistant, invasive and recurrent characteristics to MB. In our study, we evaluated the effects of Pimavanserin (PVT) in MB. Our results demonstrated that PVT treatment suppressed the proliferation of various MB cells by inducing apoptosis as shown by AnnexinV APC-PI assay. At molecular level, PVT inhibits Lyn/STAT3/MBSCs signaling axis. Additionally, chronic administration of PVT significantly suppressed the growth of subcutaneous and intracranial tumor xenografts without causing major side effects. Taken together, our study provides convincing evidence that PVT could serve as a novel treatment option for MB patients in the future. Ours is the first study to report to report the anti-cancer effects of PVT. Citation Format: Sharavan Ramachandran, Shreyas Gaikwad, Sanjay K. Srivastava. Pimavanserin suppresses the growth of medulloblastoma by inhibiting Lyn/STAT3/MBSC signaling axis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3896.