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Cancer chemoprevention: scientific promise, clinical uncertainty


We review fundamental processes, such as mutation, oxidative stress, and inflammation that are critical for carcinogenesis and provide specific molecular targets for new chemopreventive agents. New information from molecular biology studies has identified such targets, including regulatory molecules such as Nrf2 (nuclear factor erythroid 2-related factor 2), epidermal growth factor receptor kinases, phosphatidylinositol 3-kinase, components of the Janus kinase–signal transducers and activators of transcription (JAK–STAT) pathway, nuclear factor-κB, and cyclin D. The development of new drugs for the control of these targets that are both safe and effective will be important for the future of cancer chemoprevention.

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Figure 1: For men and women in the US, younger than 85 years, death rates from heart disease have dropped markedly since 1975, while overall death rates from cancer have shown relatively little change.
Figure 2: A simplified diagram of the mechanisms that can activate the transcription factor, Nrf2.
Figure 3: The concept of 'health' needs to consider future events, not just the immediate present.


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We thank Carl Nathan, Paul Talalay, Thomas Kensler, Anita Roberts, and Clifton Leaf for valuable discussions. Megan Padgett has provided expert assistance in the preparation of this review. Supported by grants from the National Cancer Institute (CA-78814), the National Foundation for Cancer Research, and members of the Dartmouth College Class of 1934.

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Correspondence to Michael B Sporn.

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Sporn, M., Liby, K. Cancer chemoprevention: scientific promise, clinical uncertainty. Nat Rev Clin Oncol 2, 518–525 (2005).

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