Sphingosine-1-phosphate In Cancer Research Articles

Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer.

In recent years, newly emerging therapies, such as immune checkpoint inhibitors and antibody-drug conjugates, have further improved outcomes for breast cancer patients. However, recurrent and metastatic breast cancer often eventually develops resistance to these drugs, and cure is still rare. As such, the development of new therapies for refractory breast cancer that differ from conventional mechanisms of action is necessary. Sphingosine-1-phosphate (S1P) is a key molecule with a variety of bioactive activities, including involvement in cancer cell proliferation, invasion, and metastasis. S1P also contributes to the formation of the cancer microenvironment by inducing surrounding vascular- and lymph-angiogenesis and regulating the immune system. In this article, we outline the basic mechanism of action of S1P, summarize previous findings on the function of S1P in cancer cells and the cancer microenvironment, and discuss the clinical significance of S1P in breast cancer and the therapeutic potential of targeting S1P signaling.

Recent advances in the role of sphingosine 1‐phosphate in cancer

Sphingosine 1-phosphate (S1P) is a bioactive lipid that binds to a family of G protein-coupled receptors (S1P1-5 ) and intracellular targets, such as HDAC1/2, that are functional in normal and pathophysiologic cell biology. There is a significant role for sphingosine 1-phosphate in cancer underpinning the so-called hallmarks, such as transformation and replicative immortality. In this review, we survey the most recent developments concerning the role of sphingosine 1-phosphate receptors, sphingosine kinase and S1P lyase in cancer and the prognostic indications of these receptors and enzymes in terms of disease-specific survival and recurrence. We also provide evidence for identification of new therapeutic approaches targeting sphingosine 1-phosphate to prevent neovascularisation, to revert aggressive and drug-resistant cancers to more amenable forms sensitive to chemotherapy, and to induce cytotoxicity in cancer cells. Finally, we briefly describe current advances in the development of isoform-specific inhibitors of sphingosine kinases for potential use in the treatment of various cancers, where these enzymes have a predominant role. This review will therefore highlight sphingosine 1-phosphate signalling as a promising translational target for precision medicine in stratified cancer patients.

Does the Sphingosine 1-Phosphate Receptor-1 Provide a Better or Worse Prognostic Outcome for Breast Cancer Patients?

Recently, Lei et al., (2018) published an article in Cancer Medicine claiming a survival benefit of sphingosine 1-phosphate (S1P) and sphingosine 1-phosphate receptor 1 (S1P1) expression in breast cancer patients. This controversial study opposes the prevailing view concerning the deleterious role of S1P in cancer. This is discussed in depth in the current opinion article.

Sphingosine‐1‐phosphate antibodies as potential agents in the treatment of cancer and age‐related macular degeneration

Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid thought to be dysregulated in a variety of disease conditions. In this review, we discuss the roles of S1P in cancer and in wet age-related macular degeneration. We also explore potential treatment strategies for these disorders, including the utility of anti-S1P antibodies acting as molecular sponges to neutralize dysregulated S1P in relevant tissues.