title: COX-2 inhibitor as a radiation enhancer: new strategies for the treatment of lung cancer.
abstract: Lung cancer is one of the most common causes of cancer-related mortality throughout the world, and the incidence continues to increase. Smoking is the number one cause of lung cancer. Emerging data have implicated cyclooxygenase-2 (COX-2) and prostanoid production in the pathogenesis of lung carcinoma. In invasive lung tumors, COX-2 upregulation has been reported in up to 90% of cases. COX-2 upregulation is an early event in the development of non-small-cell lung cancer and may be integral to the development of new blood vessels and production of specific proteases that are critical to growth and spread of lung malignancies. COX-2 inhibitors are known to enhance the chemosensitivity in COX-2 overexpressing lung cancer cell lines. Recently, we have demonstrated that selective COX-2 inhibitors also enhance the effect of radiation in COX-2 overexpressed cells. Therefore, inhibitors of COX-2 in combination with chemoradiation therapy may be an alternative strategy that can be tested in clinical trials. The combination of COX-2 inhibitors and radiation suggest a complementary strategy to target angiogenesis while potentially minimizing the impact on quality of life. Currently, several groups are conducting clinical trials in cervix cancer, lung cancer, and brain tumors, using inhibitors of COX-2 in combination with chemotherapy and radiation therapy. These clinical trials will help to elucidate the role of this interesting class.
authors.affiliation: Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-5671, USA.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Saha
authors.forename: Hongryull
authors.initials: H
authors.lastname: Pyo
authors.forename: Hak
authors.initials: H
authors.lastname: Choy
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000502:physiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D008565:Membrane Proteins; D009389:Neovascularization, Pathologic; D009578:Nitrobenzenes / Q000494:pharmacology / Q000627:therapeutic use; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D015854:Up-Regulation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011453:Prostaglandins; D011838:Radiation-Sensitizing Agents; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases