Selenium supplementation may increase the efficacy of cetuximab in metastatic colorectal cancer patients.
Recently, cyclooxygenase-2 (COX-2) inhibitor therapy has emerged as a possible new approach to the prevention and treatment of colorectal cancer (CRC). The COX enzymes (COX-1 and COX-2) are key enzymes of prostaglandin (PG) biosynthesis and are overexpressed in approximately 80% of human CRCs. Presumably, bioactive lipid products of COX, such as PGE(2), are responsible for some of the pro-neoplastic effects mediated by this enzyme. The early effects of COX-2-derived PGE(2) are in part mediated by the epidermal growth factor receptor (EGFR). Selenomethionine decreases COX-2 protein and PGE(2) levels. Cetuximab is a chimeric IgG1 monoclonal antibody that binds to EGFR with high specificity thus blocking ligand-induced phosphorylation of EGFR. Cetuximab has clinically significant activity when given alone or in combination with irinotecan in patients with irinotecan-refractory CRC. We suggest that selenium supplementation by decreasing the COX-2 protein and PGE-2 levels in cancer cells may increase efficacy of cetuximab in advanced CRC patients.
Altundag
Kadri
K
Department of Medical Oncology, Hacettepe University, Faculty of Medicine, Sihhiye, 06100 Ankara, Turkey. drkadri@usa.net
Silay
Yavuz S
YS
Altundag
Ozden
O
Yigitbasi
Orhan G
OG
Gundeslioglu
Ozlem
O
Gunduz
Mehmet
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology / Q000556:secondary*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000473:pathology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003864:Depression, Chemical; D019587:Dietary Supplements; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D006801:Humans; D000077146:Irinotecan; D008565:Membrane Proteins; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010766:Phosphorylation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012645:Selenomethionine / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D012645:Selenomethionine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D066246:ErbB Receptors; D012643:Selenium; D015232:Dinoprostone; D000068818:Cetuximab; D002166:Camptothecin