Sphingosine Kinase Shows Promise as New Target for Viral Lymphomas
A new paper from researchers at Louisiana State University Health Sciences Center, is the first to report that sphingolipids, specialized fat molecules, are vital to the survival of aggressive lymphomas caused by viruses. The paper, published in the January issue of Molecular Cancer Therapeutics, also identifies a small molecule inhibitor of the sphingosine kinase (SPHK) that shows promise for treating these lymphomas.
The paper focuses on primary effusion lymphoma (PEL), a rare HIV-associated non-Hodgkin’s lymphoma for which the average survival rate is 6 months. The current standard of care for PEL is a combination of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), chemotherapy, and antiretroviral therapy (for those that are HIV positive). However, side effects and drug resistance (generated through virus-associated mechanisms) continue to limit the effectiveness of standard therapy.
Overexpression of SPHK occurs in a variety of cancers, and its phosphorylation of sphingosine results in accumulation of sphingosine-1-phosphate (S1P) and activation of antiapoptotic signal transduction. After documenting this vital role of SPHK in PEL tumors, the researchers tested a novel clinical grade small molecule, ABC294640 (developed by Apogee Biotechnology Corporation), that selectively targets SPHK and has shown previous antitumor effects for kidney, prostate, and breast cancer cell lines.
Results show that ABC29460 induced apoptosis of PEL cells through inhibition of signal transduction activated by SPHK. The results also show that ABC294640 worked selectively for virus-infected cells while sparing uninfected cells.
Dr. Chris Parsons, Director of the HIV Malignancies Program at LSU Health Sciences Center and senior author of the paper says that while it is still early in their understanding of how these special lipids contribute to viral cancers, “This is a major potential advance. There are no therapies available to fight viral tumors by selectively blocking these pathways, all while not harming normal, uninfected cells.”
