Cyclooxygenase-2 as a potential target in the prevention and treatment of genitourinary tumors: a review.
OBJECTIVE
Recent years have seen a dramatic expansion in our discovery and knowledge of the molecular mechanisms of cancer development and progression. The discovery and elucidation of prostaglandin pathways, in particular the molecular and clinical role of cyclooxygenase (COX)-2 function, has had important application to neoplasms. Current understanding of the role of COX-2 activity and, thereby, the potential clinical usefulness of COX-2 specific inhibitors as they apply to urological oncology are discussed.


METHODS
The discovery of prostaglandin pathways, the molecular and clinical role of COX-2 function, and the corresponding application to neoplasms were reviewed in the scientific literature (MEDLINE from 1960 to the present). In particular, a thorough review of the current literature and recent abstract presentations at scientific meetings was done regarding the potential role of COX-2 in urological cancers (MEDLINE from 1960 to the present, and American Urological Association and American Society of Clinical Oncology annual meeting abstracts from1998 to the present).


RESULTS
Decreased apoptosis, increased angiogenesis and immunosuppression are just some of the known sequelae of COX-2 over expression and each effect may have an important role in tumor formation and progression. Preclinical research and pilot clinical studies in urological oncology, in particular prostate, bladder and kidney cancer, have proved to be quite promising to date.


CONCLUSIONS
Currently we are just beginning to understand the molecular mechanisms and clinical effects of COX-2 function and inhibition, and the potential for COX-2 specific inhibitors to affect potentially tumor biology and growth and, thereby, serve as antitumor drugs with therapeutic and chemopreventive roles for urological cancers. The absence of complete scientific understanding in these areas provides a generous opportunity for innovative and important scientific study.
Pruthi
Raj S
RS
Division of Urologic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Derksen
Eric
E
Gaston
Kris
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000502:physiology*; D007680:Kidney Neoplasms / Q000188:drug therapy; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy; D014565:Urogenital Neoplasms / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases