Related Experiment Video
Updated: Dec 1, 2025
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Therapeutic potential of Fingolimod in triple negative breast cancer preclinical models
Tristan Rupp1, Océane Pelouin1, Laurie Genest1
1Porsolt SAS, ZA de Glatigné, 53940 Le Genest-Saint-Isle, France.
Abstract:
Surgery followed by a chemotherapy agent is the first-line treatment for breast cancer patients. Nevertheless, new targets are required for women with triple-negative breast cancer (TNBC) in order to improve the treatment of this aggressive cancer subtype. Multiple pro-inflammatory molecules including lipid-based substances such as sphingosine-1-phosphate (S1P) promote cancer progression. In this preclinical study, we aim to investigate the efficacy of Fingolimod, an inhibitor of S1P / S1P receptors axis, already approved as an immunomodulator in multiple sclerosis. The impact of Fingolimod was analyzed using in vitro 2D and 3D cell survival analysis and in vivo orthotopic graft models, using mouse and human TNBC cells implanted in immunocompetent or immunodeficient mice, respectively. Resection of the tumor primary mass was also performed to mimic the clinical standard of care. We demonstrated that Fingolimod repressed tumor cell survival in vitro. We also showed in preclinical mouse TNBC models that Fingolimod repressed tumor progression and liver and spleen metastases without apparent adverse effects on the animals. Our data indicate that Fingolimod induces tumor cells apoptosis and thereby represses tumor progression. Globally, our data suggest that Fingolimod merits further evaluation as a potential therapeutic opportunity for TNBC.
Insights
Fingolimod, an S1P receptor inhibitor, shows promise in treating triple-negative breast cancer (TNBC) by reducing tumor progression and metastasis. This preclinical study suggests Fingolimod could be a new therapeutic option for aggressive TNBC.
Area of Science:
- Oncology
- Pharmacology
- Immunology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype requiring novel therapeutic targets.
- Pro-inflammatory molecules, including sphingosine-1-phosphate (S1P), contribute to cancer progression.
- Current treatments for TNBC often involve surgery and chemotherapy, necessitating alternative strategies.
Purpose of the Study:
- To investigate the efficacy of Fingolimod, an S1P receptor axis inhibitor, as a potential treatment for TNBC.
- To evaluate Fingolimod's impact on TNBC cell survival and tumor progression in preclinical models.
Main Methods:
- In vitro 2D and 3D cell survival assays were performed.
- Preclinical orthotopic graft models using mouse and human TNBC cells were established.
- Tumor progression, metastasis, and adverse effects were assessed in vivo following tumor resection.
Main Results:
- Fingolimod demonstrated significant repression of TNBC cell survival in vitro.
- In vivo studies showed Fingolimod inhibited tumor progression and reduced liver and spleen metastases.
- No apparent adverse effects were observed in the animal models treated with Fingolimod.
Conclusions:
- Fingolimod induces apoptosis in tumor cells, thereby repressing TNBC progression.
- Fingolimod exhibits potential as a therapeutic agent for TNBC, warranting further clinical evaluation.
- Targeting the S1P axis with Fingolimod offers a novel strategy against aggressive TNBC.
