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Sphingosine kinase 2 inhibitor slowed the growth of castration resistant prostate cancer cells

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 Jan 29, 2016 Researchers at the Medical University of South Carolina (MUSC) announced the results of preclinical in vitro and in vivo studies being published in December 2015 issue of Molecular Therapeutics which stated that the growth of castration-resistant prostate cancer can be slowed down by first-in-class sphingosine kinase 2 inhibitor by inhibiting the enzyme dihydroceramide desaturase (DEGS).

The study was led by Christina Voelkel-Johnson, Ph.D., and an associate professor of Microbiology and Immunology at MUSC. A pilot grant from MUSC Hollings Cancer Center funded the study. The compound was developed by Charles D. Smith, Ph.D. who also led phase-1 trial at MUSC Hollings Cancer Center. The techniques to use MALDI mass spectroscopy to measure sphingosine levels was developed by Michael Lilly, MUSC Health oncologist and Richard Drake, Director of Proteomics Core at MUSC.

Sphingosine kinase inhibitors are the drugs that reduced the production of sphingosine-1-phosphate.cancer cell growth and survival is promoted by this lipid signalling molecule, ultimately supporting the resistance development to chemotherapy. It was shown by the study reported in Molecular Cancer Therapeutics that YELIVA compound slowed down the proliferation of prostate cancer cells by inhibiting sphingosine kinase 2. Voelkel-Johnson said that “the compound unexpectedly also inhibited a second sphingosine enzyme which increases the level of another lipids- dihydroceramide, thereby contributing to growth suppressive effects of drugs.

This study for first time showed that YELIVA potentially links to inhibition of DEGS to slow the proliferation and growth of castration-resistant prostate cancer cells. It was shown by the in vitro studies conducted on castration-resistant mouse prostate cancer cells that YELIVA treatment reduced the expression of oncogene c-Myc and androgen receptor, which are crucial therapeutic targets for prostate cancer.   

According to Pharmaion, ”Global Prostate Cancer Therapeutics Market Opportunities, 2011 - 2021”, these findings of new drugs might prove to be novel therapeutics for advanced prostate cancer. 


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