UC Irvine

BACKGROUND AND OBJECTIVE: Globally, colorectal cancer (CRC) is the third most commonly diagnosed cancer. CRC is known to arise from precancerous polyps known as adenomas. Although there are genetic syndromes (i.e., familial adenomatous polyposis syndrome) that carry a high lifetime risk of CRC, the majority of CRC cases are sporadic. Sporadic CRC develops via molecular events that occur early and frequently in the transformation of the normal colon epithelium to invasive cancer. Prevention of sporadic CRC (i.e., CRC chemoprevention) has been a topic of interest in the past decades due to its large public health burden. The objective of this study is to review various chemopreventive agents studied in randomized controlled trials (RCTs) to evaluate their effectiveness and safety in preventing sporadic CRC. METHODS: This review focuses on recent RCTs using potential chemopreventive agents to prevent sporadic CRC formation, either directly or through reduction of its known precursors such as adenomas or aberrant crypt foci (ACF) through interventions including nonsteroidal anti-inflammatory drugs (NSAIDs), vitamins and minerals, and metabolic agents. KEY CONTENT AND FINDINGS: Multiple RCTs have been conducted in sporadic CRC chemoprevention. NSAIDs have proven promising in sporadic CRC chemoprevention but have been limited due to increased cardiovascular risk, particularly for celecoxib and rofecoxib. CONCLUSIONS: There is active investigation into establishing the first sporadic CRC chemoprevention strategy. Building from previous trials, the choice of study population, selection of endpoints, safety and tolerability, availability of surrogate biomarkers, and novel mechanisms of action targeting the adenoma-carcinoma sequence remain important points to consider for all future trials of sporadic CRC chemoprevention.