Although COX-2 up-regulation in cancer cells has been classically linked to the activation of oncogenes or transcription factors, it has been also detected in tumor cells and other cells of tumor stroma in response to hypoxia, via stabilization of hypoxia inducible factor 1 (HIF-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)25, 26, 49. This evidence concerns the gene PTGS2 and cancer.