This chapter briefly summarizes the current knowledge about the role of nonsteroidal anti-inflammatory drugs (
NSAIDs), specially focusing on those selective for
cyclooxygenase (COX)-2 (
coxibs), on
colorectal cancer (CRC) onset, and progression. Both epidemiological and experimental studies have reported that these drugs reduce the risk of developing colonic
tumors. However, the promising use of
coxibs in
chemoprevention was halted abruptly due to the detection on enhanced cardiovascular (CV) risks. Thus, we discuss the clinical data and plausible mechanisms of CV hazards associated with traditional
NSAIDs and
coxibs. The extent of inhibition of COX-2-dependent
prostacyclin, an important vasoprotective and anti-thrombotic pathway, in the absence of a complete suppression of COX-1-dependent platelet function, at common doses of
NSAIDs, might play a role in CV toxicity.
Coxibs might still be reserved for younger patients with
familial adenomatous polyposis (FAP). However, it should be taken into consideration that recent findings of enhanced
thromboxane (TX)A(2) biosynthesis in colon
tumorigenesis, detected in humans. In this context, the use of low-dose
aspirin (which mainly acts by inhibiting platelet COX-1-dependent TXA(2)) may have a place for
chemoprevention of
CRCs (see also Chap. 3 ). The possible use of
coxibs to prevent CRC will depend mainly on research progresses in
biomarkers able to identify the patients uniquely susceptible to developing thrombotic events by inhibition of COX-2.