Cyclooxygenase-2 (COX-2)--a therapeutic target in liver cancer?
Targeting COX-2, a key-enzyme of the prostaglandin metabolism, for the treatment of cancer has been in the focus of researchers for about a decade. However, only recently has this topic been related to hepatocellular carcinoma (HCC). HCC is one of the most common cancers and a growing health problem worldwide. At present, only few promising treatment options are available, accentuating the urgent need for novel therapeutic approaches. Since the first report of COX-2 overexpression in HCC, several findings support the notion that selective COX-2 inhibition proves to be beneficial in this malignancy. This review focuses on recent discoveries regarding the pro-tumorigenic potential of COX-2 in HCC and the functional effects of COX-2 inhibition on molecular mechanisms of this malignancy. Of clinical interest, promising data from in vivo experiments and case studies suggest a beneficial effect of COX-2 inhibitors for HCC- therapy. Detailed analysis of COX-2- activated pathways and related mechanisms may enable the evaluation and design of even more specific and combinatorial treatment approaches in the future.
Department of General Pathology, University Hospital, INF 220/221, 69120 Heidelberg, Germany.
Marco
M
Breinig
Peter
P
Schirmacher
Michael André
MA
Kern
D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000453:epidemiology / Q000276:immunology / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000517:prevention & control; D011453:Prostaglandins / Q000378:metabolism; D015398:Signal Transduction
D052246:Cyclooxygenase 2 Inhibitors; D011453:Prostaglandins; D051546:Cyclooxygenase 2