The Role of S1P in Multiple Myeloma Progression

Jessica Yang, Grade 12, St. Clement’s School, Sun Life Gene Medical Science Institute Cancer Research Program Student, Toronto, Ontario, Canada 

Abstract Multiple Myeloma (MM) is a blood cancer of the bone marrow that develops when malignant plasma cells overproduce abnormal proteins. MM can lead to long-term problems like anemia, impaired immunity, and organ damage. Disease progression and drug resistance are significant barriers preventing MM from being curable. Studies have highlighted sphingosine-1-phosphate’s (S1P) role in regulating cancer cell proliferation and angiogenesis. Increased levels of this bioactive sphingolipid and the abnormal activation of its receptors (S1PRs) have been found to promote MM development and reduce cells’ sensitivity to anti-myeloma drugs. Recent preclinical research has found that targeting the S1P signalling pathway with S1P receptor antagonists such as fingolimod, and with inhibitors of sphingosine kinases (SphK1 and SphK2), may suppress MM growth and induce apoptosis. However, mechanisms affecting S1P’s role in MM and its integration into existing treatments remain insufficiently understood. This review will discuss the structure and function of S1P, the role of S1P signalling in MM progression, and its implications on drug resistance.  

Keywords: Sphingosine-1-phosphate (S1P); Sphingosine-1-phosphate receptors (S1PR); Sphingosine kinase 1 (SphK1); Sphingosine kinase 2 (SphK2); Multiple myeloma (MM)