Chemoprevention
Definition
Chemoprevention involves the use, in healthy people, of natural or laboratory made substances to prevent cancer or reduce cancer risk both in high-risk individuals as well as in the general population. The aim is to reduce the cancer burden in humans. Most work is being done to reduce the risk for oral cancer, prostate cancer, cervical cancer, lung cancer, colorectal cancer, and breast cancer. The first chemopreventive agent to reach the clinic – and possibly the best known – was tamoxifen, which has been shown to cut breast cancer incidence in high-risk women by 50%. It was followed by finasteride, found to reduce prostate cancer incidence by 25% in men at high risk for the disease. However, the large-scale trials that confirmed these benefits brought to light a troublesome issue: the drugs caused serious side effects in some patients. This is an issue of particular concern when considering long-term administration of a drug to healthy people who may or may not develop cancer. Obviously, this is raising a number of ethical issues. An effective chemopreventive agent should not significantly alter quality of life, and should be ideally inexpensive, safe, well tolerated, and effective in preventing more than one cancer.
Experience with celecoxib (Celebrex) and other COX-2 inhibitors illustrates the importance of an assessment of the risk/benefit ratio for patients. COX-2 inhibitors have shown impressive efficacy in the prevention of colon cancer and several other forms of cancer, but they also increase the risk of serious cardiovascular side effects.
Attention has focused on nutraceuticals and phytochemicals as chemopreventive agents. Curcumin (found in the curry spice turmeric), has shown dramatic anticancer results in preclinical studies owing to its significant anti- inflammation properties. Curcumin has been used for thousands of years in the diets of people in the Middle and Far East and therefore is believed to have a low probability of serious side effects. Under investigation for their potential in breast cancer chemoprevention are Aromatase Inhibitors, a class of estrogen blockers, which are approved to treat metastatic breast cancer in post-menopausal women. While the idea of cancer chemoprevention is extremely attractive, much research remains to be done to make this a generally applicable option for reducing the human cancer burden. An important element will be to identify informative biomarkers to assess individual cancer risk and to possibly provide information of patients tolerance towards individual chemopreventive agents.