Chemoprevention of colorectal cancer: Past, present, and future

Abstract

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.

Searching for Drug Synergy Against Cancer Through Polyamine Metabolism Impairment: Insight Into the Metabolic Effect of Indomethacin on Lung Cancer Cells

“…A large body of evidence supports the use of NSAIDs as a chemopreventive tool in patients at high risk of colon cancer (Mohammed et al, 2018;Umezawa et al, 2019). One of the modes of action proposed for NSAIDs in this setting is overexpression of the SSAT enzyme (Turchanowa et al, 2001;Babbar et al, 2003;Babbar et al, 2006a).…”

The effects of flaxseed and tamoxifen on the inflammatory microenvironment in normal breast tissue and in breast cancer

“…Several malignancies, such as gastric and colon cancer, are preceded by chronic inflammation, which supports the concept of inflammation as a major risk factor in cancer progression (87). The role of inflammation in cancer development is also suggested by epidemiological studies showing potential effects of NSAIDs in reducing the risk of colon and breast cancer (12,217,244). Furthermore, inflammation in manifest tumors is, with almost no exceptions, associated with more aggressive disease and worse prognosis (14,15,90).…”

Drug repositioning in cancer: The current situation in Japan

“…Aspirin induces apoptosis via both COX‐dependent and COX‐independent mechanisms to combat malignancies . The details of clinical trials for aspirin are reviewed elsewhere …”

“…These anticancer effects are mainly mediated by activation of AMPK, which inhibits mTOR, a key mediator of the phosphatidylinositol 3‐kinase/Akt signaling pathway in tumor cells that activates the tumor suppressor p53, leading to cancer cell apoptosis . Details of clinical trials of metformin are reviewed elsewhere …”