TGF-beta signalling-related markers in cancer patients with bone metastasis.
We measured transforming growth factor (TGF)-beta-dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF-beta 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-beta1 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-beta inhibitor.
Baselga
Jose
J
Vall d'Hebron University Hospital, Barcelona, Spain.
Rothenberg
Mace L
ML
Tabernero
Josep
J
Seoane
Joan
J
Daly
Thomas
T
Cleverly
Ann
A
Berry
Brandi
B
Rhoades
Susanne K
SK
Ray
Chad A
CA
Fill
Jeffrey
J
Farrington
Daphne L
DL
Wallace
Lisa Anne
LA
Yingling
Jonathan M
JM
Lahn
Michael
M
Arteaga
Carlos
C
Carducci
Michael
M
D000368:Aged; D015415:Biomarkers; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy / Q000556:secondary*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000097:blood; D008297:Male; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000097:blood; D010978:Platelet Factor 4 / Q000097:blood; D015398:Signal Transduction; D051785:Smad Proteins / Q000097:blood; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000097:blood*
D015415:Biomarkers; D017370:Interleukin-11; D044162:Parathyroid Hormone-Related Protein; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D010978:Platelet Factor 4