Colorectal Cancer Chemoprevention: A Dream Coming True?

Abstract

Colorectal cancer (CRC) is one of the deadliest forms of cancer worldwide. CRC development occurs mainly through the adenoma-carcinoma sequence, which can last decades, giving the opportunity for primary prevention and early detection. CRC prevention involves different approaches, ranging from fecal occult blood testing and colonoscopy screening to chemoprevention. In this review, we discuss the main findings gathered in the field of CRC chemoprevention, focusing on different target populations and on various precancerous lesions that can be used as efficacy evaluation endpoints for chemoprevention. The ideal chemopreventive agent should be well tolerated and easy to administer, with low side effects. Moreover, it should be readily available at a low cost. These properties are crucial because these compounds are meant to be used for a long time in populations with different CRC risk profiles. Several agents have been investigated so far, some of which are currently used in clinical practice. However, further investigation is needed to devise a comprehensive and effective chemoprevention strategy for CRC.

Keywords: chemoprevention; colorectal cancer; precancerous lesions; target populations.

Figure 1

CRC tumorigenesis and chemoprevention. (A) Schematic representation of the adenoma-carcinoma sequence, which includes the progression steps, such as aberrant crypt foci (ACF) and adenoma lesions, that are used as endpoints in clinical trials to evaluate potential chemopreventive agents. (B) Chemopreventive agents are natural and synthetic compounds intended to delay cancer onset, reverse the carcinogenesis process, and prevent tumor recurrence and metastasis. The ideal chemopreventive agent should be well tolerated, safe, easy to administer, and readily available at low cost. Moreover, chemopreventive agents should be tailored to individuals at high (carriers of genetic syndromes predisposing to CRC, such as Lynch syndrome, all different types of FAP syndrome, MUTYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, and hamartoma tumor syndrome, patients with diabetes mellitus), moderate (subjects with a prior diagnosis of colonic adenoma or a family history of CRC), or average (general population, with particular concern for non-Hispanic Black men and individuals with an unhealthy diet) risk of developing CRC (B). Created with Biorender.com.