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Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer—A Plan to Move Forward

Authors' Affiliations: ¹ National Cancer Institute, Bethesda, Maryland; ² University of Texas M.D. Anderson Cancer Center, Houston, Texas; ³ Weill Medical College of Cornell University, New York, New York; ⁴ CCS Associates, Mountain View, California; ⁵ Eli Lilly & Co., Indianapolis, Indiana; ⁶ Fred Hutchinson Cancer Research Center, Seattle, Washington; ⁷ Fox Chase Cancer Center; ⁸ The Wistar Institute, Philadelphia, Pennsylvania; ⁹ University of Arizona, Tucson, Arizona; ¹⁰ Emory University, Atlanta, Georgia; ¹¹ University of Pittsburgh, Pittsburgh, Pennsylvania; ¹² International Epidemiology Institute, Rockville, Maryland; ¹³ Mayo Clinic, Rochester, Minnesota; ¹⁴ British Columbia Cancer Agency, Vancouver, British Columbia, Canada; ¹⁵ University of California at Los Angeles, Los Angeles, California; ¹⁶ University of California at Irvine, Irvine, California; ¹⁷ Baylor Sammons Cancer Center, Texas Oncology, PA, U.S. Oncology, Dallas, Texas; and ¹⁸ Johns Hopkins University, Baltimore, Maryland

Requests for reprints: Gary J. Kelloff, National Cancer Institute, Executive Plaza North, Room 6058, 6130 Executive Boulevard, Rockville, MD 20852. Phone: 301-594-0423, Fax: 301-480-3507; E-mail: kelloffg{at}mail.nih.gov.

This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.

Commentary

Progress in Chemoprevention: AACR Task Force Report

Paul F. Engstrom
Clin. Cancer Res. 2006 12: 3645. [Full Text] [PDF]

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