Repurposing Pimavanserin, an Anti-Parkinson Drug for Pancreatic Cancer Therapy

ABSTRACT: Despite major advances in cancer treatment, pancreatic cancer is still incurable and the treatment outcomes are limited. The aggressive and therapy-resistant nature of pancreatic cancer warrants the need for novel treatment options for pancreatic cancer management. Drug repurposing is emerging as an effectual strategy in the treatment of various diseases, including cancer. In the present study, we evaluated the anticancer effects of pimavanserin tartrate (PVT), an antipsychotic drug used for the treatment of Parkinson disease psychosis. PVT significantly suppressed the proliferation and induced apoptosis in various pancreatic cancer cells and gemcitabine-resistant cells with minimal effects on normal pancreatic epithelial cells and lung fibroblasts. Growth-suppressive and apoptotic effects of PVT were mediated by the inhibition of the Akt/Gli1 signaling axis. The oral administration of PVT suppressed subcutaneous and orthotopic pancreatic tumor xenografts by 51%–77%. The chronic administration of PVT did not demonstrate any general signs of toxicity or change in behavioral activity of mice. Our results indicate that pancreatic tumor growth suppression by PVT was orchestrated by the inhibition of Akt/Gli1 signaling. Since PVT is already available in the clinic with an established safety profile, our results will accelerate its clinical development for the treatment of patients with pancreatic cancer. Graphical Abstract Drug repurposing, a unique drug developmental strategy, can overcome the pitfalls for pancreatic cancer treatment. In this study, we discover the anticancer effects of an antipsychotic drug, pimavanserin, for pancreatic cancer. Our pre-clinical findings suggest that pimavanserin could be translated into the clinic to improve the treatment outcome of pancreatic cancer patients.

SUBMITTER: Ramachandran S 

PROVIDER: S-EPMC7527685 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature