TGF- signalling-related markers in cancer patients with bone metastasis

Abstract We measured transforming growth factor (TGF)- -dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF- inhibitors. Forty-nine patients with bone metastasis were enrolled in the study,...

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Bibliographic Details
Published in:Biomarkers 2008, Vol.13 (2), p.217-236
Main Authors: Baselga, Jose, Rothenberg, Mace L., Tabernero, Josep, Seoane, Joan, Daly, Thomas, Cleverly, Ann, Berry, Brandi, Rhoades, Susanne K., Ray, Chad A., Fill, Jeffrey, Farrington, Daphne L., Anne Wallace, Lisa, Yingling, Jonathan M., Lahn, Michael, Arteaga, Carlos, Carducci, Michael
Format: Article
Language:English
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Summary:Abstract We measured transforming growth factor (TGF)- -dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF- inhibitors. Forty-nine patients with bone metastasis were enrolled in the study, including patients with breast (n=23) and prostate cancer (n=15). Plasma TGF- 1 levels were elevated in more than half of the cancer patients (geometric mean 2.63 ng ml−1) and positively correlated with increased platelet factor 4 (PF4) levels, parathyroid-related protein (PTHrP), von Willebrand Factor (vWF) and interleukin (IL)-10. PBMC were stimulated ex vivo to determine the individual biological variability of an ex vivo assay measuring pSMAD expression. This assay performed sufficiently well to allow its future use in a clinical trial of a TGF- inhibitor.
ISSN:1354-750X
1366-5804
DOI:10.1080/13547500701676019