A new study examined whether Fingolimod, a drug originally approved to treat Multiple Sclerosis, could be repurposed to treat Adrenocortical Carcinoma. Researchers focused on the sphingolipid metabolic pathway and found that high activity of genes involved in producing Sphingosine 1 Phosphate (S1P) is linked to more advanced disease, more aggressive tumors, and poorer survival in patients with ACC.
Laboratory experiments using several ACC cell lines showed that Fingolimod significantly reduced cancer cell survival. The drug triggered cancer cell death through apoptosis and autophagy by blocking survival signaling pathways such as Akt and NF-κB. Fingolimod also reduced mitochondrial energy production and lowered the activity of key steroid-producing genes, which may help counteract the immune-suppressing effects often seen in ACC. When combined with the standard ACC drug Mitotane, the anticancer effects were even stronger.
The study also found that Fingolimod may help prevent cancer spread. In experimental models that mimic metastatic environments in the liver and lungs, the drug reduced the ability of ACC cells to migrate and invade these tissues. It also altered the lipid composition of cancer cells by increasing ceramides that promote cell death and decreasing lipids linked to tumor growth. Researchers suggest that Fingolimod could become a multi-target treatment for ACC and may be especially promising when combined with immunotherapy in future studies.