Journal
FRONTIERS IN BIOSCIENCE-LANDMARK
Volume 13, Issue -, Pages 2293-2298Publisher
FRONTIERS IN BIOSCIENCE INC
DOI: 10.2741/2843
Keywords
sphingolipids; gene therapy; acid ceramidase; review
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Funding
- NCI NIH HHS [P01 CA97132] Funding Source: Medline
- NCRR NIH HHS [C06 RR015455] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [P01CA097132] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR015455] Funding Source: NIH RePORTER
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During the last decade, sphingolipid deregulation, namely the balance between the pro-apoptotic molecule ceramide and the anti-apoptotic sphingolipid sphingosine-1- phosphate, has emerged as an important factor in cancer pathology and resistance to therapy. Thus, our research has been focused on developing drugs that are able to restore normal sphingolipid balance, precisely through increasing the levels of ceramide and decreasing sphingosine-1-phosphate. Particularly, inhibition of the ceramide metabolizing enzyme acid ceramidase, whose overexpression in cancer cells has been implicated in resistance to treatment, is proving to be an efficient and promising strategy. In this review, we consider our recent work with acid ceramidase inhibitors, in combination with radiation or gene therapy as a sensitizer that enhance cancer therapy.
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