The research in the applicant's lab has demonstrated that SK2 is overexpressed in MM and that SK2 inhibitor (ABC294640) down-regulated c-Myc expression and inhibited myeloma growth in vitro and in vivo in myeloma xenograft mouse model. In particular, sphingosine kinase 2 (SK2) provide a potential site for manipulation of the ceramide/sphingosine 1-phosphate (S1P) rheostat that regulates the balance between tumor cell proliferation and apoptosis, as well as tumor sensitivity to drugs and radiation.
Sphingolipid metabolism is increasingly recognized as a key pathway in tumor biology. There is an unmet medical need for the development of novel therapeutic agents that do not share similar mechanism of action with these agents.
MM remains an incurable disease, and nearly all MM patients will eventually relapse and develop resistance to currently available agents including newer proteasome inhibitors (carfilzomib) and immunomodulatory agents (pomalidomide). Multiple myeloma (MM) is the second most common hematological malignancy in the United States where it accounts for about 11,000 deaths annually.
