ArticleSurgery2026
A novel therapeutic approach to adrenocortical carcinoma repurposing fingolimod to target sphingolipid metabolism in metastatic disease.
Article in Surgery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionPatients with advanced adrenocortical carcinoma have poor survival and show elevated steroid production. Lipid metabolic profiling of adrenocortical carcinoma has revealed that the upregulation of sphingolipid metabolism, which regulates steroid synthesis, is linked to worse overall survival. Therefore, fingolimod, a Food and Drug Administration-approved drug that targets sphingolipid metabolism, represents a promising option for targeting adrenocortical carcinoma and metastatic spread.
methodsAdrenocortical carcinoma cell lines were cultured in an appropriate medium. Cell-TiterGlo assessed cell viability. Western-blot and RNA-sequencing examined the targeted pathways. Migration and invasion using decellularized extracellular matrix evaluated metastasis. Seahorse measured metabolic flux. Reverse transcription-polymerase chain reaction determined steroidogenic genes. Mass spectrometry analyzed alterations in sphingolipids.
resultsFingolimod treatment resulted in half-maximal inhibitory concentration (IC
conclusionFingolimod induces apoptosis in adrenocortical carcinoma cells by targeting sphingolipid metabolism and prevents liver and lung metastatic invasion in vitro. Further in vivo validation studies alone or in combination with immune checkpoint inhibitor will support its clinical translation as a novel repurposed therapy in adrenocortical carcinoma.
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