Acid ceramidase inhibition: a novel target for cancer therapy.
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.
Liu
Xiang
X
Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Elojeimy
Saeed
S
Turner
Lorianne S
LS
Mahdy
Ayman E M
AE
Zeidan
Youssef H
YH
Bielawska
Alicja
A
Bielawski
Jacek
J
Dong
Jian-Yun
JY
El-Zawahry
Ahmed M
AM
Guo
Gui-wen
GW
Hannun
Yusuf A
YA
Holman
David H
DH
Rubinchik
Semyon
S
Szulc
Zdzislaw
Z
Keane
Thomas E
TE
Tavassoli
Mahvash
M
Norris
James S
JS
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017727:Chicken anemia virus / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D053222:Fas Ligand Protein / Q000378:metabolism; D002517:Galactosylgalactosylglucosylceramidase / Q000037:antagonists & inhibitors*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy* / Q000628:therapy*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; D002517:Galactosylgalactosylglucosylceramidase