The National Cancer Institute's (NCI) Division of Cancer Prevention has recently funded six new consortium of research centers to conduct early phase cancer prevention clinical trials rapidly and efficiently. The more than $42 million of funding will allow the 6 institutions (see box) to assess the cancer preventive potential of new agents over the next three years.
"We wanted, and now have, a clinical trials infrastructure that lets us rapidly conduct phase II clinical trials to assess the efficacy of cancer prevention agents," said Leslie Ford, MD, associate director for clinical research in NCI's Division of Cancer Prevention. "The consortium system decreases the time between idea and conduct of a trial, allowing NCI to respond quickly to fill in research gaps and to guide the development of the field of chemoprevention."
"Each of these institutions was selected based on its proven ability to conduct cancer prevention research," said Dr. Ford. The consortium members will:
- Design and conduct early-phase clinical trials to assess the cancer prevention potential of a variety of agents, many of which target specific molecules known to be expressed in precancerous conditions.
- Characterize the effects of these agents on endpoints associated with cancer development (such as cell proliferation, apoptosis [programmed cell death], growth factor expression [growth factors are produced by the body to control growth, division, and maturation of cells and influence the growth of some cancers], oncogene expression [oncogenes are the mutated and/or overexpressed version of a normal gene that can change a normal cell into a tumor cell]) and correlate these effects with clinical endpoints.
- Develop scientific insights into the mechanisms of cancer prevention by assessing the clinical effects of these candidate agents, and by testing novel markers that may be used to determine response to the agents.
The consortium institutions each have their own networks of participating institutions to allow them to carry out clinical trials within specific populations quickly, without recreating relationships each time they want to begin a study. Each consortium member will design and implement numerous studies on agents that may play a role in preventing cancer. Among these agents are likely to be:
- Cyclooxygenase (COX) inhibitors. Because the COX enzymes are produced by many precancerous tissues, a variety of compounds that inhibit enzyme activity or expression are of interest in cancer prevention. Observational studies suggest that aspirin and selective COX-2 inhibitors (celecoxib, rofecoxib) can prevent certain cancers. Moreover, inhibitors of COX have proven activity against premalignant colorectal polyps. Other agents within this diverse class of compounds, including nitric oxide- (NO-) NSAIDs (nonsteroidal anti-inflammatory drugs), may also prevent disease and thereby justify further study.
- Statins. This class of drugs that blocks cholesterol production by inhibiting the enzyme HMG-CoA reductase is commonly used as a treatment for heart disease; the statins may play a role in cancer prevention as well. Statins that are already in use for heart disease are potential candidates for prevention studies.
- Tea Polyphenols. The relationship between tea consumption and human cancer has been studied in several different populations and at various cancer sites, with differing outcomes. In animal studies, different tea extracts, tea polyphenol mixtures, purified tea components, and tea infusions have been shown to prevent cancers of the colon, esophagus, liver, stomach, lung, breast, pancreas, and skin. Epigallocatechin gallate (EGCG), Polyphenon E (a polyphenol mixture containing EGCG), and other tea-related compounds are candidates for further study.
- Soy Isoflavones. A group of compounds found in and isolated from the soybean, isoflavones function as antioxidants and possess other activities that may result in cancer prevention. Initial studies of soy isoflavone mixtures containing genistein, daidzein, and glycitein have found them safe for human use and make them candidates for further prevention study.
The new consortium members have already submitted ideas for their first round of trials, which are under review at NCI. Studies will be selected and are expected to be underway by September 2004.
The new consortium members and principal investigators are:
- University of Arizona (Tucson, Arizona)--David Alberts, MD
- University of California-Irvine (Irvine, California)--Frank Meyskens, MD
- Northwestern University (Chicago, Illinois)-- Raymond C. Bergan, MD
- Mayo Clinic Foundation (Rochester, Minnesota)-- Charles Loprinzi, MD
- University of Texas MD Anderson Cancer Center (Houston, Texas)--Scott Lippman, MD
- University of Wisconsin-Madison (Madison, Wisconsin)--Howard Bailey, MD
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