Published online Apr 14, 2014. doi: 10.3748/wjg.v20.i14.3835
Revised: November 27, 2013
Accepted: January 3, 2014
Published online: April 14, 2014
Recent epidemiological studies, basic research and clinical trials on colorectal cancer (CRC) prevention have helped identify candidates for effective chemopreventive drugs. However, because of the conflicting results of clinical trials or side effects, the effective use of chemopreventive drugs has not been generalized, except for patients with a high-risk for developing hereditary CRC. Advances in genetic and molecular technologies have highlighted the greater complexity of carcinogenesis, especially the heterogeneity of tumors. We need to target cells and processes that are critical to carcinogenesis for chemoprevention and treatment of advanced cancer. Recent research has shown that intestinal stem cells may serve an important role in tumor initiation and formation of cancer stem cells. Moreover, studies have shown that the tumor microenvironment may play additional roles in dedifferentiation, to enable tumor cells to take on stem cell features and promote the formation of tumorigenic stem cells. Therefore, early tumorigenic changes of stem cells and signals for dedifferentiation may be good targets for chemoprevention. In this review, I focus on cancer stem cells in colorectal carcinogenesis and the effect of major chemopreventive drugs on stem cell-related pathways.
Core tip: To develop optimal chemopreventive agents, we need to target cells and pathways that are essential and critical to carcinogenesis: early tumorigenic changes of stem cells and signals for dedifferentiation may be good targets for chemoprevention. Major chemopreventive drugs, such as non-steroidal anti-inflammatory drugs, statins, proliferator-activated receptor γ agonists and metformin, have cancer stem cell (CSC)-suppressing effects via regulation of stem cell-regulating pathways, stem cell niche in the tumor microenvironment, and altered tumor metabolism. These stem cell-related steps in tumorigenesis could be critical targets for chemoprevention and CSC-targeted adjunctive treatment of colorectal cancer.