Acid ceramidase inhibition: a novel target for cancer therapy

• Published in: Frontiers in bioscience Vol. 13; no. 13; pp. 2293 - 2298
• Main Authors: Liu, Xiang, Elojeimy, Saeed, Turner, Lorianne S, Mahdy, Ayman E M, Zeidan, Youssef H, Bielawska, Alicja, Bielawski, Jacek, Dong, Jian-Yun, El-Zawahry, Ahmed M, Guo, Gui-wen, Hannun, Yusuf A, Holman, David H, Rubinchik, Semyon, Szulc, Zdzislaw, Keane, Thomas E, Tavassoli, Mahvash, Norris, James S
• Format: Journal Article
• Language: English
• Published: United States 01-01-2008
• Subjects: Animals; Antineoplastic Agents - therapeutic use; Chicken anemia virus - genetics; Enzyme Inhibitors - pharmacology; Fas Ligand Protein - metabolism; Galactosylgalactosylglucosylceramidase - antagonists & inhibitors; Genetic Therapy - methods; Genetic Vectors - metabolism; Humans; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - radiotherapy; Neoplasms - therapy
• ISSN: 1093-9946; 1093-4715
• DOI: 10.2741/2843

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 over-expression 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.