Prevention and Intervention Trials for Colorectal Cancer

Abstract

There have been a number of candidates for chemopreventive agents from synthetic drugs and natural compounds suggested to prevent colorectal cancer. However, they have shown modest efficacy in humans. The reason for this could be partly explained by the use of inappropriate models in vitro and in vivo, and the limitation of chemoprevention trials. In Japan, there are no cancer chemopreventive medicines, and few cancer chemoprevention trials to date. In contrast, an increase in the prevalence of colorectal cancer in Japan has forced us to develop more efficient chemopreventive strategies. It is now a good time to review in detail the current status and future prospects for chemoprevention of colorectal cancer with respect to the future development of chemopreventive medicines, particularly using synthetic drugs and natural compounds in Asian populations. The role and mode of action of available synthetic drugs, mainly aspirin and metformin, are reviewed. In addition, the possible impact of natural compounds with anti-inflammatory/immunosuppressive properties, such as v3 polyunsaturated fatty acid and lactoferrin, are also reviewed.

Spontaneous regression of colon cancer

“…Epidemiologic and retrospective studies have demonstrated that metformin which is an oral antidiabetic drug decreases incidence rate of colorectal cancer potentially (18). Although the patient took metformin for 15 years, it is difficult to confirm that metformin has played an important role in this regression.…”

Screening of Alternative Drugs to the Tumor Suppressor miR-375 in Esophageal Squamous Cell Carcinoma Using the Connectivity Map

“…Recently, we have revealed that both of the mRNA and protein expression of E-cadherin were upregulated with metformin-treated ESCC cells (data not shown). On the other hand, some meta-analyses also epidemiologically proved that metformin could reduce mortality and incidence rates of several cancers such as colorectal cancer and hepatocellular carcinoma [24]. Moreover, it is established that metformin shows high safety for nondiabetic patients.…”

Current Status Of Nonsteroidal Anti-inflammatory Drugs In Colorectal Cancer Prevention

“…However, NSAID antineoplastic effect may be also exerted through COX independent mechanisms, including other specific drug targets such as NF-KB, caspases, PDEs, survinin, protein kinases etc. [5,7,8,10] Indirect effect on COX has been also reported specifically for aspirin (besides inhibitory action) through the anti-platelet activity of the drug. [7] Therefore, NSAID chemopreventive mechanism is likely dual: some effects derived from the fundamental anti-inflammatory activity (through COX inhibition), while others appear to be unrelated to this propertysuppressing neoplasia through different pathways.…”

“…[10] Supportive Arguments (1-2 bleeds / 10.000 person-years) toxicity. [2,7] Regarding cardiovascular toxicity from selective COX-2 inhibitors, shorter treatment duration appears as a relatively safe (specifically for celecoxib administration in individuals with low cardiovascular risk) and potentially effective option[1, 3,5] (although the antineoplastic effect may attenuate and vanish soon after interruption of this particular treatment [7,8], likely being rather cytostatic than cytotoxic [5]). …”