Abstract LB-047: Novel anti-psychotic drug for pancreatic cancer treatment

Abstract

Abstract Pancreatic cancer is one of the most deadly malignancy with a five-year survival rate of 7%. Despite advances in cancer treatment, this disease is still incurable and the treatment outcomes are limited. Few studies have shown that neuroleptic drugs exert better anti-proliferative effects in pancreatic cancer cells when compared to conventional chemotherapeutic agents gemcitabine and oxaliplatin. In the current study, we evaluated the anti-cancer effects of pimavanserin, an anti-psychotic drug used for the treatment of Parkinson's disease psychosis. Pimavanserin significantly suppressed the proliferation of AsPC1, BxPC3, PANC1, MIAPaCa2 and PO2 pancreatic cancer cells with the IC50 between 3 - 9µM at 24, 48 and 72 hours. Pimavanserin treatment induced 2-5 fold apoptosis in pancreatic cancer cells. Notably, no significant cell death was observed in normal human pancreatic ductal epithelial (HPDE-6) cells by pimavanserin treatment. Furthermore, pimavanserin treatment inhibits the expression of key oncogenic proteins and cancer stem cell markers such as pAkt(S473), pSTAT3(Y705), β-catenin, GLI-1, GLI-2, c-Myc, Oct-4, SOX-2, NANOG and CD44. We further evaluated the efficacy of pimavanserin in two different in vivo tumor models. Oral administration of 10mg/kg pimavanserin suppressed 50% of sub-cutaneously implanted BxPC3 tumors in athymic nude mice. In another setting, 10mg/kg pimavanserin by oral gavage inhibited the growth of orthotopically implanted PANC1 pancreatic tumors by 75%. Moreover, chronic administration of pimavanserin did not show any general signs of toxicity and no apparent changes were observed in the behavioral activity of mice. Further mechanistic studies are in progress. Since pimavanserin is already available in the clinic with established safety profile, our results will accelerate its clinical development for treatment of patients with pancreatic cancer. Our study is the first to demonstrate the anti-cancer effects of pimavanserin. Citation Format: Sharavan Ramachandran, Sanjay K. Srivastava. Novel anti-psychotic drug for pancreatic cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-047.