Editorial [Hot Topic: Cyclooxygenase-2 Inhibitors and Cancer (Guest Editor: J.-P. Henichart)]

The discovery of an inductible form (COX-2) of cyclooxygenases expressed in inflamed tissue lead to the rapid development of selective COX-2 inhibitors [1], denominated coxibs and expected to be useful in the treatment of pathologies such as arthritis without gastrointestinal toxicity compared with non-steroid-antiinflammatory drugs (NSAIDs) which inhibit the gastric mucosal protection assumed by COX-1 isoform [2]. However, the observation in randomised controlled trials that long-term rofecoxib use was associated with an enhanced risk of significant cardiovascular side-effects (myocardial infarction and stroke) [3], lead to its withdrawing. Nevertheless, another important function of COX-2 was found in term of cell proliferation and several lines of evidence suggest the critical role of COX-2 in tumorigenesis [4,5] and thus selective COX-2 inhibitors become promising as anticancer drugs. To bring to light this potential therapeutic strategy considering COX-2 as a key target, it seemed necessary to examine the occurrence of the enzyme in different cancer cell types and its role in apoptosis, angiogenesis, together with the impact of metabolites such as prostaglandins (PGE2, PGD2...) in the cell proliferation or cell invasion. It is important to give some information concerning the control of COX-2 expression during carcinogenesis and protumorigenic activity of COX-2 before to detail the importance of coxibs in prostate, colon (see the article of Hénichart'team), lung (see the article of Dubinett'team), breast (see the article of Brueggemeier'team). The pharmacology of coxibs (celecoxib and analogues) and nimesulide (see the article of Pirotte'team) is thus important to consider to evaluate their potential anticancer properties and in this perspective the choice of adequate models appears to be crucial. Molecular interactions (see the article of Chavatte'team), inhibition properties measurements [6], cellular evaluations (choice of the representative cancer cell lines) and animal studies [7-9] have to be well-designed. In addition, coxib-based combinations, including the association with aromatase inhibitors, farnesyltransferase inhibitors, tyrosine kinase inhibitors, for therapy of advanced cancers and in chemoprevention should be tried in view to increase the efficacity and decrease side-effects detected in the coxibs. References [1] Luong, C.; Miller, A.; Barnett, J.; Chow, J.; Ramesha, C.; Browner, M.F. Nat. Struct. Biol., 1996, 3, 927. [2] Vane, J. Nature, 1994, 367, 215. [3] Fitzgerald, G.A. N. Engl. J. Med., 2004, 351, 1709. [4] Cao, Y.; Prescott, S.M. J. Cell Physiol., 2002, 190, 279. [5] Evans, J.F.; Kargman, S.L. Curr. Pharm. Des., 2004, 10, 627. [6] Pommery, J.; Pommery, N.; Hénichart, J.P. Prostaglandins Leukot. Essent. Fatty Acids, 2005, 73, 411. [7] Hull, M.A.; Ko, S.C.; Hawcroft, G. Mol. Cancer Ther., 2004, 3, 1031. [8] Chulada, P.C.; Thompson, M.B.; Mahler, J.F.; Doyle, C.M.; Gaul, B.W.; Lee, C.; Tiano, H.F.; Morham, S.G.; Smithies, O.; Langenbach, R. Cancer Res., 2000, 60, 4705. [9] Oshima, M.; Dinchuk, J.E.; Kargman, S.L.; Oshima, H.; Hancock, B.; Kwong, E.; Trzaskos, J.M.; Evans, J.F.; Taketo, M.M. Cell, 1996, 87, 803.