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

Jose Baselga, Mace L. Rothenberg, Josep Tabernero, Joan Seoane, Thomas Daly, Ann Cleverly, Brandi Berry, Susanne K. Rhoades, Chad A. Ray, Jeffrey Fill, Daphne L. Farrington, Lisa Anne Wallace, Jonathan M. Yingling, Michael Lahn, Carlos Arteaga, Michael Carducci

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

We measured transforming growth factor (TGF)-β-dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF-β 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-β1 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-β inhibitor.

Original languageEnglish (US)
Pages (from-to)217-236
Number of pages20
JournalBiomarkers
Volume13
Issue number2
DOIs
StatePublished - Mar 2008

Keywords

  • Cancer
  • Plasma biomarkers
  • TGF-β

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Health, Toxicology and Mutagenesis

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