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Cancer refers to a diverse group of diseases characterized by the unchecked proliferation of cells and the formation of solid tumors that infiltrate and destroy the surrounding normal tissue. Chemoprevention is defined by the U.S. National Cancer Institute as “the use of natural or synthetic substances to reduce the risk of developing cancer or to reduce the chance that cancer will recur”. No single prevention strategy will stop the mutagenic and mitogenic cellular events that precede the development of cancer. For example, it was once thought that increased antioxidant intake would protect against cancer. Environmental carcinogens often increase the intracellular production of reactive oxygen species (ROS) that induce DNA damage and mutation. While antioxidants reduce the cellular levels of ROS in vitro, their impact on cancer incidence is inconclusive. Antioxidants may reduce ROS-induced DNA damage in normal cells, preventing carcinogenesis. However, antioxidants may also promote proliferation of mutagenic precancerous cells by preventing ROS-induced apoptosis. Further, high levels of cellular antioxidants can counteract antitumor agents whose efficacy depends, in part, on the production of ROS.
Often chemoprevention can be demonstrated in animal models of carcinogenesis, but clinical chemoprevention is less concrete. Members of epidemiological studies or clinical trials do not have a uniform risk of developing cancer, and differences observed between treatment groups must be statistically valid to demonstrate chemopreventive activity. Tamoxifen, a selective estrogen response modifier (SERM) that blocks the activity of estrogen receptors in breast tissue has demonstrated chemopreventive activity in clinical trials. Tamoxifen decreases the recurrence of estrogen-sensitive breast cancers in patients and reduces the incidence of breast cancer in women with high risk factors. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown in clinical studies to reduce the incidence of colorectal polyps that are often a precursor to cancer. Other substances, including foods, food components, dietary supplements, and herbal constituents, have also been investigated for possible chemopreventive activity.
Chemopreventive Agents
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