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) and their affiliates to evaluate 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, growth factor expression, oncogene expression) 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. In consultation with NCI, each consortium member will design and implement numerous studies on agents that may play a role in preventing cancer. Among the agents that will be under study or are under consideration for study are:
- 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. Aspirin and celecoxib have already been shown to inhibit carcinogenesis in clinical trials, and celecoxib is being evaluated in combination with other drugs for colorectal and breast cancer prevention. Other agents within this diverse class of compounds, including nitric oxide- (NO-) NSAIDS and other prescription drugs, may also act as chemopreventive agents and may be studied.
- Statins. A class of drugs that blocks cholesterol production by inhibiting the enzyme HMG-CoA reductase is commonly used as a treatment for cardiovascular disease; by virtue of their effect on key metabolic steps leading to cancer, statins alone and in combination 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 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 currently being tested for chemopreventive efficacy.
- Soy Isoflavones. A group of compounds 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.
These classes of compounds represent just a few of the many agents being tested or with potential for future testing. Agents are selected based on their potential efficacy in healthy individuals at risk for cancer and their low toxicity over an extended period of time.
Following a meeting with members of the NCI Division of Cancer Prevention, the new consortium members submitted ideas for their first round of trials. Studies 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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