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Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Preclinical Pancreatic Cancer Models
Pauline Gousseau1, Laurie Genest1, Guillaume Froget1
1Porsolt SAS, ZA de Glatigné, Oncology Group, Le Genest-Saint-Isle, 53940, France.
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 respective in vitro cytotoxicity and in vivo antitumor effects.
Methods:
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.
Results:
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.
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.
Insights
Fingolimod and Dimethyl Fumarate show potential against pancreatic cancer. These drugs demonstrated anticancer effects in preclinical models, offering new therapeutic possibilities for this challenging disease.
Area of Science:
- Oncology
- Pharmacology
Background:
- Pancreatic cancer has a low five-year survival rate, with current treatments like chemotherapy and radiotherapy offering limited clinical benefits.
- Novel therapeutic strategies are crucial for improving outcomes in pancreatic cancer patients.
- Fingolimod and Dimethyl Fumarate (DMF), established treatments for multiple sclerosis, have demonstrated preclinical anti-cancer properties.
Purpose of the Study:
- To evaluate the therapeutic potential of Fingolimod and Dimethyl Fumarate (DMF) in pancreatic cancer.
- To investigate the in vitro cytotoxicity and in vivo antitumor effects of Fingolimod and DMF in pancreatic cancer models.
Main Methods:
- Utilized 3D spheroid tumor models for in vitro evaluation of Fingolimod and DMF.
- Assessed in vivo antitumor effects in subcutaneous xenograft models using pancreatic cancer cell lines (PANC-1 and CFPAC-1).
- Compared the efficacy of Fingolimod and DMF against standard-of-care treatments, Gemcitabine and Erlotinib.
Main Results:
- Both Fingolimod and DMF induced significant cytotoxicity in pancreatic cancer spheroids in vitro.
- Fingolimod and DMF exhibited notable anticancer effects in vivo xenograft models.
- Observed responses with Fingolimod and DMF were comparable to those of Gemcitabine and Erlotinib.
Conclusions:
- Fingolimod and DMF show emerging potential as novel therapeutic agents for pancreatic cancer.
- These findings warrant further investigation into the mechanisms by which Fingolimod and DMF influence pancreatic tumor progression.
- Further research is necessary to fully characterize the anti-cancer activity of Fingolimod and DMF in pancreatic cancer.
