Abstract
Substantial efforts are underway for prevention of early stages or recurrence of colorectal cancers (CRC) or new polyp formation by chemoprevention strategies. Several epidemiological, clinical and preclinical studies to date have supported the chemopreventive potentials of several targeted drug classes including non-steroidal anti-inflammatory drugs (NSAIDs) (aspirin, naproxen, sulindac, celecoxib, and licofelone), statins and other natural agents—both individually, and in combinations. Most preclinical trials although were efficacious, only few agents entered clinical trials and have been proven to be potential chemopreventive agents for colon cancer. However, there are limitations for these agents that hinder their approval by the food and drug administration for chemoprevention use in high-risk individuals and in patients with early stages of CRC. In this review, we update the recent advancement in pre-clinical and clinical development of selected anti-inflammatory agents (aspirin, naproxen, sulindac, celecoxib, and licofelone) and their combinations for further development as novel colon cancer chemopreventive drugs. We provide further new perspectives from this old research, and insights into precision medicine strategies to overcome unwanted side-effects and overcoming strategies for colon cancer chemoprevention.
Highlights
Colorectal cancer (CRC), is the third most common cancer among men and women, and is a preventable cancer once identified at early stages through different chemoprevention strategies [1,2]
The results obtained in the Meyskens et al [109] study involving 375 patients, the DFMO plus sulindac drug combination reduced the overall incidence of adenoma recurrence by 70%, from 41% in the placebo group to 12% with the combination treatment [109,110]
Unresolved questions with regard to efficacy, safety, optimal treatment regimen, and mechanism of action limit the clinical utility of non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of CRC in patients
Summary
Colorectal cancer (CRC), is the third most common cancer among men and women, and is a preventable cancer once identified at early stages through different chemoprevention strategies [1,2]. Several previous studies suggested that NSAIDs can prevent risk factors-associated CRC [11,12]. CRC development, like many other cancers is a slow process that takes several years for initiation to precursor lesion formation to progression into adenoma, carcinoma, invasion and metastasis [16,17]. Targeting tumor-associated inflammation is one of the strategies for colon cancer prevention [7]. Number of targeted agents was evaluated clinically for chemoprevention of CRC after successful preclinical studies. We review molecular targets, preclinical trials, efficacies, clinical trials, toxicities and limitations of the aforementioned NSAIDs. we will provide our views and throw light on some future precision medicine approaches for colon cancer chemoprevention
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