[Cyclooxygenase 2 and breast cancer. From biological concepts to therapeutic trials].
Cyclooxygenases (Cox) are prostaglandin synthetase enzymes which play a key role in mammary carcinogenesis. Several connections were demonstrated between Cox and a few oncogenes (v-src, v-Ha-ras, HER-2/neu, Wnt, p53 mutated), alimentary products (PUFAs), transcription factors (c-jun and c-fos), proapoptotic proteins [Bax et Bcl-x(L)] or antiapoptotic (Bcl-2), CYP19 aromatase gene, NFkappaB receptor (RANKL), angiogenesis (via VEGF, TXA2, oxid nitric synthetase, alphaVbeta3 integrin receptor), peroxisome gamma proliferator receptor (PPARgamma) and its ligand PGJ2 and with antitubuline chemotherapy drugs. No correlation of Cox2 expression with hormonal receptors was shown. In epidemiologic studies there is evidence of breast cancer risk reduction for women who take AINS for a long time. Alimentary factors like resveratrol or insaturated fat acid reduce Cox2 expression in animal and could be investigated in human studies. Clinical trials are planed with the anti Cox2 celecoxib for breast cancer prevention, in adjuvant setting, in metastatic situation combined with exemestane or antitubulin drugs or in neoadjuvant therapy.
Guastalla
Jean-Paul
JP
Centre Léon-Bérard, 28, rue Laennec, 69008 Lyon. guastall@lyon.fnclcc.fr
Bachelot
Thomas
T
Ray-Coquard
Isabelle
I
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011720:Pyrazoles; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013449:Sulfonamides / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D018719:Erb-b2 Receptor Tyrosine Kinases; D013449:Sulfonamides; C496540:PTGS2 protein, human