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Paving the Way
CHORI Study Highlighted on Cover of Cancer Prevention Research

CHORI scientist Ervin Epstein, MD, has just published what peer reviewers are calling an elegant series of studies, featured on the cover of the January issue of Cancer Prevention Research, and accompanied by two editorial reviews. The first study to investigate cyclooxygenase (COX) inhibitors for the prevention of skin cancer, Dr. Epstein's publication is causing quite a stir in the field of cancer prevention.

"We feel the most significant aspect is that the results we found in our mouse models were duplicated in the clinical studies. This strongly argues that we have a successful study model in which we can test other cancer prevention strategies."


Researchers in the field of chemoprevention - or cancer prevention - have been searching for decades for a non-toxic drug that could be given to prevent the development of cancer at the outset.

"The most successful example of preventative pharmacology is the statins. You take a statin, your cholesterol falls and your chances of dying from atherosclerosis fall as well. That's what we're all looking for - an extraordinarily safe preventative cancer drug," explains Dr. Epstein.

Basal cell carcinoma (BCC), one of the most common forms of skin cancer, develops sporadically in a million individuals in the United States every year. Although BCC rarely spreads through the rest of the body or is fatal, it is a malignant tumor that requires a great deal of medical attention. BCC and squamous cell carcinomas , a similar cancer of the skin, together represent the 5th largest cancer cost for Medicare. Finding a preventative treatment for skin or other types of cancer as safe and effective as statins are for heart disease has proven to be an incredible challenge, however.
"There have been an unfortunate number of clinical trials testing different cancer prevention strategies that have been staggeringly expensive and were shown in the end to have absolutely no benefit."

As Dr. Epstein explains, "In some cases, prevention strategies resulted in negative affects, even though there were data and good rationales based for instance on strong hints from epidemiologic studies to suggest they would work. No one can afford those kinds of studies anymore."

The challenge with many of these studies has been two-fold. First, conducting cancer prevention studies in the general population that yield significant enough results requires thousands of participants over the course of anywhere from 5 to 15 years - and the funding to conduct a study of that magnitude.

Second, the study results that have provided the foundation for the clinical trials often are achieved in animal models that unfortunately do not always provide an accurate refection of the human environment in which cancers actually develop.

Dr. Epstein's series of studies has made waves however, because it overcame both these challenges by focusing on a rare condition called Basal Cell Nevus Syndrome (BCNS), in which patients develop the same skin cancer as in the sporadic form, but with tumors numbering in the hundreds of thousands.
"By studying patients with the syndrome, we can study a reasonable number of patients - in this case 60, and follow them for a reasonable amount of time, in this case 3 years, and still get statistically significant numbers because of the large number of cancers each of these unfortunate individuals gets."

In addition, because BCNS is caused by a genetic mutation - first identified by a group of researchers including Dr. Epstein - it is possible to genetically engineer mouse models that have the same mutation that causes BCNS, thereby closely duplicating natural skin tumor development in a study environment for the first time.

"We were able to show a similar positive effect of COX inhibition in both a drug study and a genetic study in the mice, which we were then able to confirm in a clinical trial," says Dr. Epstein.

"We don't think the benefits we were able to show are worth the risks that we now know are associated with COX inhibitors, some of which were taken off the market in 2004 due to increased risk for heart attack and stroke, but it means we now have an effective model to test other preventative strategies."

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Tuesday, May 17, 2011 8:19 AM

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