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Chemoprevention to Prevent Cancer
Ernest H. Rosenbaum, MD

For years, many ways have been tried to prevent cancer, using drugs, herbs, concoctions, machines and other modalities. More recently, substantial gains have occurred in cancer prevention. The National Cancer Institute has promoted research studies to develop agents for the chemoprevention of cancer.

Waun Ki Hong, M.D., at the M.D. Anderson Hospital recognized that it takes many years of using an agent to help prevent cancer from developing. In 1990, he demonstrated chemoprevention for head and neck malignancies, using vitamin A analogs, which suppressed and inhibited cancer growth and differentiation of both malignant and pre-malignant cells. Many diseases, such as hypertension and heart disease, are treated with drugs to lower cholesterol and control hypertension, for example.

Tamoxifen, for instance, has been shown to reduce the incidence of high-risk breast cancer women by 50%. Prostate cancer risk can be reduced by about 25% using Finasteride, but the side effects are often difficult to manage, especially for healthy people who are only at risk. Thus, it is important to select those at very high risk and target this population for chemopreventive trials and treatment.

With colon cancer, for example, prevention with COX2 inhibitors, such as celecoxib (Celebrex), has been successful, but the risk of cardiovascular disease as a side effect has led to its limited use. Celebrex works as an anti-inflammatory drug, which blocks the cyclooxygenase-2 enzyme, which is overproduced when cells are inflamed and could be the precursor of a cancerous process. The M.D. Anderson study showed a 36% reduction in the development of colon adenomas and a 50% reduction in larger, more dangerous adenomas using Celebrex.
Reference: Oncolog, an M.D. Anderson Cancer Center publication, University of Texas, October 2007, vol. 52, #10, pg. 1-3.

Celebrex for colon cancer prevention is still under study. Families with familial adenomatous polyposis (FAP), with hundreds of precancerous polyps in the colon and rectum, is a population at very high risk, meriting chemoprevention using drugs such as Celebrex in children with FAP, to help delay or control growth of adenomatous polyps.

For breast cancer, Raloxifene (Evista) is comparable to Tamoxifen for women with estrogen receptor-positive breast cancer in helping prevent invasive breast cancer with a decreased incidence of about 50%. These SERMs (selective estrogen receptive modulators) block the estrogen effect, which helps promote breast cancer growth. Tamoxifen has the advantage of decreasing the risk of non-invasive breast cancer, which Raloxifene does not do, but has the increased side effect of uterine cancer, stroke and blood clots. Studies are now being done on aromatase inhibitors to prevent breast cancer compared to Tamoxifen and Raloxifene.

Trials are now being conducted on:
1. Erlotinib, a targeted human epidermal growth factor receptor molecule that inhibits tumor growth for persons at high risk for oral cancer.
2. Baby aspirin is being used in a trial for colon cancer prevention similar to that for prevention of cardiovascular disease and strokes. Early data shows a reduction in precancerous colon polyps by 19% for those with a strong family history. The side effect risks include gastrointestinal bleeding and stroke.
3. Calcium along with vitamin D is being used for osteoporosis prevention, as well as being evaluated in studies for a reduction in colon and rectum adenoma formation.
4. The curry spices have curcumin, which has anticancer properties by reducing the inflammatory process and appears to have few side effects.

Obviously, chemoprevention is a new, recent approach to cancer prevention, and current studies are being done to evaluate its effectiveness; although, several studies have shown that it has a definite role.