A high-quality body of evidence supports the use of
aspirin in reducing sporadic and hereditary
adenomatous polyps, and numerous observational studies point to a reduction in
colorectal cancer (CRC) risk. However, using
aspirin as an adjuvant
therapy in established CRC was until recently inconceivable. Now, evidence from both observational and clinical trials of
aspirin for other indications suggests that
aspirin initiation after (or before) the diagnosis of CRC improves CRC-specific mortality. These exciting findings need to be confirmed in prospective randomized trials that are underway. The recent failure of adjuvant
irinotecan,
bevacizumab, and
cetuximab clinical trials compels us to reconsider our assumptions and paradigms for treating CRC. In this Review, we summarize clinical and preclinical evidence supporting
aspirin use in established CRC and outline a framework for better understanding
aspirin activity in the pathogenesis of CRC. We describe the data supporting adjuvant
aspirin in resected CRC, including the issues of dose, duration and toxicity, and discuss potential
biomarkers that may help better select patients for
aspirin therapy.