Years of research come to fruition with launch of oral cancer prevention trial.

Although news headlines and research dollars have focused largely on advances made in cancer treatments, prevention researchers are hard at work developing methods to stop cancer early — before it can even be called cancer. Lippman, professor of medicine and cancer prevention and chair of the Department of Clinical Cancer Prevention at the University of Texas M. D. Ander-son Cancer Center in Houston, and his colleagues have been working for many years on strategies to delay oral cancers and, as a culmination of those efforts, will launch a chemoprevention trial early this year. Like others in the prevention fi eld, Lippman is capitalizing on advances in tumor biology to redesign prevention trials, which traditionally have been known for their many participants, long duration, and high costs. He and his colleagues are fi guring out ways to lower these numbers as well as the risk to the participants. One strategy is to better defi ne the high-risk populations who participate in the trials and to use more targeted therapies that may increase anticancer effects with fewer side effects. Since most interventions are likely to have some side effects, it is critical to treat people at greatest risk who stand to gain the most from the intervention and to avoid treating those unlikely to develop the disease. But fi nding factors that predict who is at high risk for oral cancer has not been easy. Tobacco and alcohol use are the major risk factors for oral squa-mous cell carcinoma, the most common head and neck cancer, which accounts for more than 300,000 new cancer cases annually worldwide. But even tobacco and alcohol use are not specifi c enough risk factors to identify a truly high-risk population. Molecular markers for oral cancer have also been investigated. During oral carcinogenesis, the normal mucosa in the mouth develops into intraepithe-lial neoplasia (IEN); these may progress to red patches (erythroplakia) and fi nally to squamous cell carcinoma or invasive cancer. During this process, alterations of several tumor suppressor genes (FHIT, p16, and p53) occur, and cyclin D1, cyclooxygenase 2 (COX-2), and phospho-epidermal growth factor receptor (EGFR) are overexpressed. However, most people with IEN do not develop oral squamous cell carcinoma. Although these events are essential to the understanding of the process and will help guide the choice of drug targets, so far none of these molecular markers has been shown to be a reliable predictor of …