Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer.
Many human cancers exhibit elevated prostaglandin (PG) levels due to upregulation of cyclooxygenase-2 (COX-2), a key enzyme in eicosanoid biosynthesis. COX-2 over-expression has been observed in about 40% of cases of invasive breast carcinoma and at a higher frequency in preinvasive ductal carcinoma in situ tumors, Extensive pharmacologic and genetic evidence implicates COX enzymes in neoplasia. Epidemiologic analyses demonstrate a protective effect of COX-inhibiting nonsteroidal anti-inflammatory drugs with respect to human cancer. Complementary experimental studies have established that both conventional nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors suppress mammary tumor formation in rodent breast cancer models. Furthermore, knocking out Cox-2 reduces mammary tumorigenesis and angiogenesis, and, conversely, transgenic COX-2 over-expression induces tumor formation. The utility of COX/PG signaling as a target for chemoprevention has been established by randomized controlled clinical trials. However, these studies also identified increased cardiovascular risk associated with use of selective COX-2 inhibitors. Thus, current efforts are directed toward identifying safer approaches to antagonizing COX/PG signaling for cancer prevention and treatment, with a particular focus on PGE2 regulation and signaling, because PGE2 is a key pro-tumorigenic prostanoid.
Howe
Louise R
LR
Department of Cell & Developmental Biology, Weill Medical College of Cornell University, York Avenue, New York, New York 10021, USA. lrhowe@med.cornell.edu
D001943:Breast Neoplasms / Q000201:enzymology* / Q000517:prevention & control; D051546:Cyclooxygenase 2 / Q000502:physiology*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation; D011453:Prostaglandins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D052246:Cyclooxygenase 2 Inhibitors; D011453:Prostaglandins; D051546:Cyclooxygenase 2