Non-steroidal anti-inflammatory drugs to potentiate chemotherapy effects: from lab to clinic.
Most solid tumors express the cyclooxygenase-2 (COX-2) protein, a target of NSAIDs. COX-2 overexpression in tumorsis considered a predictor of more advanced stage disease and of worse prognosis in a number of studies investigating solid malignancies. Therefore, NSAIDs are evaluated as anti-cancer drugs. NSAIDs inhibit proliferation, invasiveness of tumors, and angiogenesis and overcome apoptosis resistance in a COX-2 dependent and independent manner. This review will focus on the rationale behind NSAIDs, including selective COX-2 inhibitors, in combination with conventional chemotherapeutic drugs or novel molecular targeted drugs. Studies investigating anti-cancer effects of NSAIDs on cell lines and xenograft models have shown modulation of the Akt, NF-kappaB, tyrosine kinase and the death receptor-mediated apoptosis pathways. COX-2 expression in tumors is not yet used as biomarker in the clinic. Despite the increased risk on cardiovascular toxicity induced by selective COX-2 inhibitors, several ongoing clinical trials are still investigating the therapeutic benefits of NSAIDs in oncology. The anti-tumor effects in these trials balanced with the side effects data will define the precise role of selective COX-2 inhibitors in the treatment of cancer patients.
de Groot
D J A
DJ
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
de Vries
E G E
EG
Groen
H J M
HJ
de Jong
S
S
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D052246:Cyclooxygenase 2 Inhibitors; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors