Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer

George Thomas, Steve Horvath, Bradley L. Smith, Katherine Crosby, Lori A. Lebel, Matthew Schrage, Jonathan Said, Jean De Kernion, Robert E. Reiter, Charles L. Sawyers

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Purpose: As kinase inhibitors transition from the laboratory to patients, it is imperative to develop biomarkers that can be used in the clinic. The primary objectives are to identify patients most likely to benefit from molecularly targeted therapies and to document modulation of the drug target. Constitutive activation of the phosphoinositide 3-kinase (PI3K) pathway and its downstream effectors, as a result of PTEN loss or by other mechanisms, occurs in a high proportion of prostate cancers, making it an ideal template for the design of clinical trials involving PI3K pathway inhibitors. Prostate cancers also present unique organ-specific challenges, in that tumors are heterogeneous and diagnostic tissue is extremely limited. Experimental Design: Working within these limitations, we have developed a set of immunohistochemical assays that define activation of the PI3K pathway in clinical samples. Results and Conclusions: Using both univariate and multivariate analyses, we show that loss of PTEN is highly correlated with the activation of AKT, and this, in turn, is associated with the phosphorylation of S6, one of its main effectors. These three antibodies are potentially able to define a molecular signature of PTEN loss and/or AKT pathway activation in prostate cancer.

Original languageEnglish (US)
Pages (from-to)8351-8356
Number of pages6
JournalClinical Cancer Research
Volume10
Issue number24
DOIs
StatePublished - Dec 15 2004
Externally publishedYes

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Critical Pathways
1-Phosphatidylinositol 4-Kinase
Prostatic Neoplasms
Antibodies
S 6
Research Design
Phosphotransferases
Multivariate Analysis
Biomarkers
Phosphorylation
Clinical Trials
Pharmaceutical Preparations
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Thomas, G., Horvath, S., Smith, B. L., Crosby, K., Lebel, L. A., Schrage, M., ... Sawyers, C. L. (2004). Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer. Clinical Cancer Research, 10(24), 8351-8356. https://doi.org/10.1158/1078-0432.CCR-04-0130

Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer. / Thomas, George; Horvath, Steve; Smith, Bradley L.; Crosby, Katherine; Lebel, Lori A.; Schrage, Matthew; Said, Jonathan; De Kernion, Jean; Reiter, Robert E.; Sawyers, Charles L.

In: Clinical Cancer Research, Vol. 10, No. 24, 15.12.2004, p. 8351-8356.

Research output: Contribution to journalArticle

Thomas, G, Horvath, S, Smith, BL, Crosby, K, Lebel, LA, Schrage, M, Said, J, De Kernion, J, Reiter, RE & Sawyers, CL 2004, 'Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer', Clinical Cancer Research, vol. 10, no. 24, pp. 8351-8356. https://doi.org/10.1158/1078-0432.CCR-04-0130
Thomas, George ; Horvath, Steve ; Smith, Bradley L. ; Crosby, Katherine ; Lebel, Lori A. ; Schrage, Matthew ; Said, Jonathan ; De Kernion, Jean ; Reiter, Robert E. ; Sawyers, Charles L. / Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 24. pp. 8351-8356.
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