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

## TL;DR

This study explores whether Fingolimod and Dimethyl Fumarate, used for multiple sclerosis, can also treat pancreatic cancer in preclinical models.

## Contribution

The first evaluation of Fingolimod and DMF in pancreatic cancer preclinical models, both in vitro and in vivo.

## Key findings

- Fingolimod and DMF showed cytotoxic effects in pancreatic cancer spheroids in vitro.
- Both drugs exhibited antitumor effects in subcutaneous xenograft models of pancreatic cancer.
- The effects of Fingolimod and DMF were comparable to standard treatments like Gemcitabine and Erlotinib.

## Abstract

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 respective in vitro cytotoxicity and in vivo antitumor effects.

In this study, we evaluated for the first time these two drugs in pancreatic preclinical models in vitro using 3D spheroid tumor models and in vivo, which are compared to two standard-of-care consisting of Gemcitabine and Erlotinib.

In vitro, 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.

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.