Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Preclinical Pancreatic Cancer Models.

Abstract

OBJECTIVES: The five-year survival rate for pancreatic cancer is notably low, posing a significant challenge to patient health. The primary treatments are radiotherapy and chemotherapy, sometimes combined with targeted therapy; however, their clinical benefits are limited. Therefore, developing new models to evaluate the therapeutic potential of novel molecules is essential. Fingolimod and Dimethyl Fumarate (DMF), currently used to treat multiple sclerosis, have recently been shown to have anti-cancer effects in several preclinical tumor models. This study aims to evaluate the therapeutic potential of Fingolimod and DMF in pancreatic cancer by investigating their respectivecytotoxicity andantitumor effects. METHODS: In this study, we evaluated for the first time these two drugs in pancreatic preclinical modelsusing 3D spheroid tumor models and, which are compared to two standard-of-care consisting of Gemcitabine and Erlotinib. RESULTS: , both Fingolimod and DMF induced cytotoxicity in spheroids from two pancreatic cell lines. Additionally, Fingolimod and DMF displayed anticancer effects in two subcutaneous xenograft models using PANC-1 and CFPAC-1 cells. CONCLUSIONS: Although the responses observed with Fingolimod and DMF were similar to those of Gemcitabine and Erlotinib, these findings indicate a potential emerging interest in Fingolimod and DMF for the treatment of pancreatic cancer. However, further work is still necessary to fully characterize how these drugs affect tumor progression.