title: Inhibition of microsomal prostaglandin E synthase-1 as targeted therapy in cancer treatment.
abstract: The bioactive lipid prostaglandin E2 (PGE2) is involved in several steps of carcinogenesis in some of the most common cancers, e.g. colon cancer, lung cancer, prostate cancer and breast cancer. Non-steroidal anti-inflammatory drugs (NSAIDs) that target cyclooxygenase (COX) activity, the first step of the PGE2 biosynthesis, has been found to reduce the incidence of colon cancer. Due to severe adverse effects on the gastrointestinal tract and the cardiovascular system, their use as chemopreventing agent has been hampered. Genetic deletion of microsomal prostaglandin E synthase-1 (mPGES-1), the enzyme responsible for the second step of the PGE2 biosynthesis, has resulted in reduced tumor progression in mouse models of colon cancer. Inhibition of mPGES-1 would potentially be beneficial to a great number of patients without the side effects associated with long-term treatment with traditional NSAIDs.
authors.affiliation: Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Larsson
authors.affiliation: Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden. Electronic address: per-johan.jakobsson@ki.se.
authors.forename: Per-Johan
authors.initials: PJ
authors.lastname: Jakobsson
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017353:Gene Deletion; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics*; D008861:Microsomes / Q000201:enzymology*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000071876:Prostaglandin-E Synthases
chemical_list: D004791:Enzyme Inhibitors; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse
keywords: Cancer treatment; Microsomal prostaglandin E synthase-1; Prostaglandin E(2); Targeted therapy