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For clinical chemoprevention trials against cancer, including colorectal cancer (<jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content>), well\u2010established biomarkers are necessary for use as reliable endpoints. Difficulty in establishing validated biomarkers has delayed the start of <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content> chemoprevention development. Chemoprevention trials for <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content> have only recently been initiated thanks to the identification of reliable biomarkers, such as colorectal adenomas and aberrant crypt foci. Some promising agents have been developed for the prevention of <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content>. The chemopreventive effect of selective cyclooxygenase 2 inhibitors has been shown, although these inhibitors are associated with cardiovascular toxicity as a crucial adverse effect. Aspirin, which is a unique agent among non\u2010steroidal anti\u2010inflammatory drugs (<jats:styled-content style=\"fixed-case\">NSAID<\/jats:styled-content>s) showing minimal gastrointestinal toxicity and no cardiovascular risk, has prevented adenoma recurrence in some randomized controlled trials. More recently, metformin, which is a first\u2010line oral medicine for type 2 diabetes, has been shown to be safe and to prevent adenoma recurrence. A recommendation of the United States Preventive Services Task Force published in 2016 provides a Grade B recommendation for the use of aspirin for chronic prophylaxis against diseases, including <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content>, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel \u201cpost\u2010aspirin\u201d agents are also needed. The combined use of multiple drugs, such as aspirin and metformin, is another option that may lead not only to stronger <jats:styled-content style=\"fixed-case\">CRC<\/jats:styled-content> prevention, but also to improvement of other obesity\u2010related diseases.<\/jats:p>","DOI":"10.1111\/cas.14149","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T14:46:10Z","timestamp":1564497970000},"page":"3018-3026","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Chemoprevention of colorectal cancer: Past, present, and future"],"prefix":"10.1111","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0251-3761","authenticated-orcid":false,"given":"Shotaro","family":"Umezawa","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Yokohama City University Yokohama 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