Cyclooxygenase in the treatment of glioma: its complex role in signal transduction.
BACKGROUND
High-grade glioma remains one of the most difficult cancers to treat. Recent studies in oncology have identified a role of the ubiquitous enzyme, cyclooxygenase (Cox), especially cyclooxygenase-2 (COX-2) in cell proliferation, and its inhibition in cancer control, apoptosis, as well as synergy with other forms of therapy. The inhibitors of the Cox enzyme are well known as members of the nonsteroidal anti-inflammatory drug (NSAID) class of pharmaceuticals.


METHODS
In vitro and in vivo studies of different cancers expressing COX-2, including glioma studies, along with the few clinical trials that have been reported are reviewed to specifically identify the actions of these agents.


RESULTS
The anticancer effect of the COX-2 inhibitors may occur irrelevant of COX-2 expression, and it appears to be drug-specific, as well as dose-specific in different cancers. In combination with chemotherapeutic agents, the COX-2 inhibitors may have an additive, synergistic, or inhibitory effect on tumor growth.


CONCLUSIONS
As evaluations of this class of drugs begin in glioma, in vitro and in vivo data should be acquired to accurately predict which compounds will have an effect in controlling tumor growth and at which doses these should be used. The actual expression and inhibition of COX-2 may not always be relevant to the effects on tumor growth.
New
Pamela
P
Department of Neurosurgery/Neuro-oncology, Baylor College of Medicine, Houston, TX 77030, USA. pnew@bcm.tmc.edu
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology / Q000532:radiotherapy; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D020156:Salicylic Acid / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D020156:Salicylic Acid; D001241:Aspirin; D007052:Ibuprofen