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Despite significant advances in cancer treatment and measures of neoplastic progression, drug effect (or early detection, overall cancer incidence has increased, pharmacodynamic markers), and markers that measure cancer-associated morbidity is considerable, and overall prognosis as well as predict responses to specific therapy. cancer survival has remained relatively flat over the past All these biomarkers have the potential to greatly augment several decades (1,2). However, new technology the development of successful chemoprevention therapies, allowing exploration of signal transduction pathways, but two specific types of biomarkers will have the most identification of cancer-associated genes, and imaging of immediate impact on successful chemopreventive drug tissue architecture and molecular and cellular function is development—those that measure the risk of developing increasing our understanding of carcinogenesis and cancer invasive life-threatening disease, and those whose mo- progression. This knowledge is moving the focus of cancer lation can “reasonably predict” clinical benefit and, therapeutics, including cancer preventive treatments, to therefore, serve as surrogate endpoints for later-occurring drugs that take advantage of cellular control mechanisms clinical disease. Thus far, the biomarker that best measures to selectively suppress cancer progression. these two phenomena is intraepithelial neoplasia (IEN) Carcinogenesis is now visualized as a multifocal, because it is a near obligate precursor to cancer.