The Importance of Sphingosine Kinase in Breast Cancer: A Potential for Breast Cancer Management.

Breast cancer management includes a combination of surgery, radiation therapy, and chemotherapy. While this management has proven effective, it is not perfect. To expand the umbrella of management to resistant breast cancer tumors, researchers have explored the idea of sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as a potential target for treatment. In this article, we review the mechanism of the sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) axis along with its effect on the tumor microenvironment (TME) and compounds that have been studied inhibiting the SphK/S1P axis. We searched for relevant articles in the last five years in Medline and PubMed Central. Inclusion criteria, exclusion criteria, and quality checklists were applied to identify the most relevant articles. We compiled the information that has been summarized in the respective tables and figures provided in this review. The metabolism of sphingolipids was summarized, followed by the SphK/S1P upregulation in breast cancer cells. The variety of effects by upregulation of SphK led to an increase in inflammation, growth, and metastasis in breast cancer tumors. The increase in S1P also impacted the TME, including the cells and surrounding tissue, allowing the breast tumors to thrive. The final point made was a summary of the compounds and drugs that inhibited the SphK/S1P axis. They have proven their effectiveness and show even greater efficacy in combination with docetaxel and doxorubicin in preclinical studies. In conclusion, what is known about the SphK/S1P axis within breast cancer cells is immense but incomplete as we summarize what is known so far. Having a complete picture will allow a faster transition to application in the clinical field but clinical trials have not commenced as of yet.