Progress in chemoprevention drug development: The promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer - A plan to move forward

Gary J. Kelloff, Scott M. Lippman, Andrew J. Dannenberg, Caroline C. Sigman, Homer L. Pearce, Brian J. Reid, Eva Szabo, V. Craig Jordan, Margaret R. Spitz, Gordon B. Mills, Vali A. Papadimitrakopoulou, Reuben Lotan, Bharat B. Aggarwal, Robert S. Bresalier, Jeri Kim, Banu Arun, Karen H. Lu, Melanie E. Thomas, Helen E. Rhodes, Molly A. BrewerMichele Follen, Dong M. Shin, Howard L. Parnes, Jill M. Siegfried, Alison A. Evans, William J. Blot, Wong Ho Chow, Patricia L. Blount, Carlo C. Maley, Kenneth K. Wang, Stephen Lam, J. Jack Lee, Steven M. Dubinett, Paul F. Engstrom, Frank L. Meyskens, Joyce O'Shaughnessy, Ernest T. Hawk, Bernard Levin, William G. Nelson, Waun Ki Hong

Research output: Contribution to journalReview article

232 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3661-3697
Number of pages37
JournalClinical Cancer Research
Volume12
Issue number12
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kelloff, G. J., Lippman, S. M., Dannenberg, A. J., Sigman, C. C., Pearce, H. L., Reid, B. J., Szabo, E., Jordan, V. C., Spitz, M. R., Mills, G. B., Papadimitrakopoulou, V. A., Lotan, R., Aggarwal, B. B., Bresalier, R. S., Kim, J., Arun, B., Lu, K. H., Thomas, M. E., Rhodes, H. E., ... Hong, W. K. (2006). Progress in chemoprevention drug development: The promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer - A plan to move forward. Clinical Cancer Research, 12(12), 3661-3697. https://doi.org/10.1158/1078-0432.CCR-06-1104