PTGS2 and colorectal carcinoma: The COX-2 fibroblast-driven adenoma-initiating pathway could be an important underlying mechanism behind the CRC-preventative effect of COX-2 inhibitors in humans [48], and might also provide a promising alternative (i.e., PTGER4 inhibition [49]) for chemoprevention of CRC given the substantial side effects of COX-inhibiting drugs [48].