The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials

D. G. Bostwick, H. B. Burke, T. M. Wheeler, L. W.K. Chung, R. Bookstein, T. G. Pretlow, R. B. Nagle, R. Montironi, M. M. Lieber, R. W. Veltri, W. E. Grizzle, D. J. Grignon

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Surrogate endpoint biomarkers (SEBs) are needed in clinical chemoprevention trials to avoid the excessively long study periods and high costs associated with the use of cancer incidence reduction as an endpoint, particularly with relatively slow-growing tumors such as prostatic adenocarcinoma. SEBs should be directly associated with the evolution of neoplasia, and develop with high frequency in abnormal cells of susceptible individuals. If SEBs can be modified by a particular intervention regimen in short-term studies, the rationale for carrying out long-term studies may be strengthened. The consensus panel identified a small and manageable group of biomarkers measured in tissue or serum as the most promising in prostate cancer chemoprevention, including (1) prostate specific antigen (PSA); (2) morphometric markers, such as nuclear size and roundness; (3) proliferation markers, such as MIB-1 and PCNA; (4) nuclear DNA content (ploidy); (5) oncogene c-erbB-2 (HER-2/neu) expression; (6) angiogenesis; and (7) high-grade prostatic intraepithelial neoplasia (PIN). Information regarding many of these and other biomarkers is limited, calling for further investigation. Also, these factors, chosen chiefly for their proven or proposed utility as prognostic factors, may be less useful as SEBs. It was agreed that concurrent study of numerous markers rather than single markers allows comparison of their relative utility, including assessment of ease of quantitation and the sensitivity, specificity, and positive and negative predictive value.

Original languageEnglish (US)
Pages (from-to)283-289
Number of pages7
JournalJournal of Cellular Biochemistry
Volume56
Issue numberSUPPL. 19
StatePublished - Jan 1 1994

Keywords

  • Biomarkers
  • Chemoprevention
  • Premalignancy
  • Prostate cancer
  • Prostatic intraepithelial neoplasia
  • Risk stratification

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Bostwick, D. G., Burke, H. B., Wheeler, T. M., Chung, L. W. K., Bookstein, R., Pretlow, T. G., Nagle, R. B., Montironi, R., Lieber, M. M., Veltri, R. W., Grizzle, W. E., & Grignon, D. J. (1994). The most promising surrogate endpoint biomarkers for screening candidate chemopreventive compounds for prostatic adenocarcinoma in short-term phase II clinical trials. Journal of Cellular Biochemistry, 56(SUPPL. 19), 283-289.