Targeting Sphingolipids in Breast Cancer: From Tumor Biology to Therapeutic Strategies

Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors. Among various regulatory molecules, sphingolipids play pivotal roles in dynamically modulating fundamental cellular processes such as proliferation, apoptosis, and metastasis through metabolic interconversions, including phosphorylation, glycosylation, and the generation of sphingosine-1-phosphate. This review aims to elucidate the mechanisms through which sphingolipid metabolism orchestrates cancer cell fate and drives breast cancer progression. Particular emphasis is placed on the balance between proapoptotic ceramides and pro-survival metabolites, such as sphingosine-1-phosphate, which collectively influence tumor growth and the therapeutic response. Additional sphingolipid species, including glucosylceramide and gangliosides (GD2, GD3, GM1, and GM3), have also been implicated in promoting breast cancer development. Furthermore, sphingolipid-based therapeutic strategies, including immunotherapy and antibody therapy, are discussed. By providing a comprehensive overview of sphingolipid metabolism, this review aims to identify novel therapeutic targets that may help overcome treatment resistance and improve clinical outcomes in breast cancer.