Chemoprevention of colorectal cancer: Past, present, and future

• Published in: Cancer science Vol. 110; no. 10; pp. 3018 - 3026
• Main Authors: Umezawa, Shotaro, Higurashi, Takuma, Komiya, Yasuhiko, Arimoto, Jun, Horita, Nobuyuki, Kaneko, Takeshi, Iwasaki, Motoki, Nakagama, Hitoshi, Nakajima, Atsushi
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2019; John Wiley and Sons Inc
• Subjects: Adenoma; Advisory Committees; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Aspirin; Biomarkers; Blood pressure; calcium; Cancer therapies; Cardiotoxicity; Cardiovascular diseases; Cardiovascular Diseases - chemically induced; chemoprevention; Chemoprevention - adverse effects; Chemoprevention - methods; Clinical trials; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - prevention & control; Cyclooxygenase 2 Inhibitors - adverse effects; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase-2; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Disease; Disease prevention; Drug dosages; Drugs; Female; Humans; Inflammation; Kinases; Male; Metformin; Mortality; Neoplasm Recurrence, Local - prevention & control; Nonsteroidal anti-inflammatory drugs; Polyps; Prevention; Prophylaxis; Randomized Controlled Trials as Topic; Review; Toxicity; Tumors; United States > US; aspirin; metformin; calcium; chemoprevention; colorectal cancer
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14149

Chemoprevention began to be considered as a potential strategy for lowering the incidence of cancer and cancer‐related deaths in the 1970s. For clinical chemoprevention trials against cancer, including colorectal cancer (CRC), well‐established biomarkers are necessary for use as reliable endpoints. Difficulty in establishing validated biomarkers has delayed the start of CRC chemoprevention development. Chemoprevention trials for CRC 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 CRC. 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‐steroidal anti‐inflammatory drugs (NSAIDs) showing minimal gastrointestinal toxicity and no cardiovascular risk, has prevented adenoma recurrence in some randomized controlled trials. More recently, metformin, which is a first‐line 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 CRC, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel “post‐aspirin” 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 CRC prevention, but also to improvement of other obesity‐related diseases. Some promising agents have been developed for the prevention of colorectal cancer (CRC), including selective cyclooxygenase 2 inhibitors, aspirin, and metformin. Draft guidelines 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 CRC, in certain select populations. However, the roles of other agents have yet to be determined, and investigations to identify novel “post‐aspirin” agents are also needed.