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

**Authors:** Min Hee Kim, Boyoon Huh, Joo-Won Park, Woo-Jae Park

PMC · DOI: 10.32604/or.2025.071523 · Oncology Research · 2026-01-19

## TL;DR

This review explores how sphingolipids influence breast cancer progression and highlights potential therapeutic strategies targeting these molecules.

## Contribution

The paper provides a comprehensive overview of sphingolipid metabolism in breast cancer and identifies novel therapeutic targets.

## Key findings

- Sphingolipid metabolism regulates cancer cell processes like proliferation and apoptosis.
- The balance between ceramides and sphingosine-1-phosphate affects tumor growth and treatment response.
- Glucosylceramide and gangliosides contribute to breast cancer development.

## Abstract

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.

## Linked entities

- **Chemicals:** sphingosine-1-phosphate (PubChem CID 5283560), glucosylceramide (PubChem CID 178331063), GD2 (PubChem CID 11966234), GD3 (PubChem CID 23982), GM1 (PubChem CID 5497107), GM3 (PubChem CID 101035653)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** GRDX (Graves disease, susceptibility to, X-linked) [NCBI Gene 117189] {aka GD3}
- **Diseases:** Breast Cancer (MESH:D001943), metastasis (MESH:D009362), Tumor (MESH:D009369)
- **Chemicals:** gangliosides (MESH:D005732), sphingosine-1-phosphate (MESH:C060506), Sphingolipids (MESH:D013107), GM3 (-), glucosylceramide (MESH:D005963), ceramides (MESH:D002518)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12848689/full.md

## References

168 references — full list in the complete paper: https://tomesphere.com/paper/PMC12848689/full.md

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Source: https://tomesphere.com/paper/PMC12848689