Inhibitors of cyclo-oxygenase 2: a new class of anticancer agents?
Experimental studies have shown that cyclo-oxygenase 2 (COX2) is involved in tumour development and progression. Selective inhibitors of COX2 (coxibs) block tumour growth through many mechanisms, especially by antiangiogenic and proapoptotic effects. In experimental models, coxibs potentiate the activity of cytotoxic agents, hormones, and radiotherapy. Large clinical studies have shown chemopreventive activity of coxibs in colorectal cancer. The findings of preclinical studies coupled with the overexpression of COX2 observed in advanced human tumours are the basis for new therapeutic anticancer strategies based on combinations of coxibs with other anticancer treatment modalities. Early clinical studies have documented the feasibility, good tolerability, and promising activity of coxibs combined with chemotherapy in patients with advanced colorectal and non-small-cell lung cancers. Here, we describe the recent findings on the antitumour effects of coxibs with particular focus on the opportunities that have emerged for treatment of cancer.
Gasparini
Giampietro
G
Division of Medical Oncology, S Filippo Neri Hospital, Rome, Italy. gasparini.oncology@tisclinet.it
Longo
Raffaele
R
Sarmiento
Roberta
R
Morabito
Alessandro
A
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008565:Membrane Proteins; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011506:Proteins / Q000627:therapeutic use; D015262:Xenobiotics / Q000378:metabolism
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; C448783:HIAF-1 protein, human; D007527:Isoenzymes; D008565:Membrane Proteins; D011506:Proteins; D015262:Xenobiotics; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases