Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer

Gordon C. Jayson (), Cong Zhou, Alison Backen, Laura Horsley, Kalena Marti-Marti, Danielle Shaw, Nerissa Mescallado, Andrew Clamp, Mark P. Saunders, Juan W. Valle, Saifee Mullamitha, Mike Braun, Jurjees Hasan, Delyth McEntee, Kathryn Simpson, Ross A. Little, Yvonne Watson, Susan Cheung, Caleb Roberts, Linda Ashcroft, Prakash Manoharan, Stefan J. Scherer, Olivia Puerto, Alan Jackson, James P. B. O’Connor, Geoff J. M. Parker and Caroline Dive
Additional contact information
Gordon C. Jayson: University of Manchester
Cong Zhou: University of Manchester
Alison Backen: Cancer Research UK Manchester Institute & Manchester Centre for Cancer Biomarker Sciences
Laura Horsley: University of Manchester
Kalena Marti-Marti: University of Manchester
Danielle Shaw: Clatterbridge Cancer Centre
Nerissa Mescallado: University of Manchester
Andrew Clamp: The Christie NHS Foundation Trust
Mark P. Saunders: The Christie NHS Foundation Trust
Juan W. Valle: University of Manchester
Saifee Mullamitha: The Christie NHS Foundation Trust
Mike Braun: The Christie NHS Foundation Trust
Jurjees Hasan: The Christie NHS Foundation Trust
Delyth McEntee: The Christie NHS Foundation Trust
Kathryn Simpson: Cancer Research UK Manchester Institute & Manchester Centre for Cancer Biomarker Sciences
Ross A. Little: University of Manchester
Yvonne Watson: University of Manchester
Susan Cheung: University of Manchester
Caleb Roberts: University of Manchester
Linda Ashcroft: The Christie NHS Foundation Trust
Prakash Manoharan: University of Manchester
Stefan J. Scherer: Novartis Pharmaceuticals Corporation
Olivia Puerto: Del Puerto Limited
Alan Jackson: University of Manchester
James P. B. O’Connor: University of Manchester
Geoff J. M. Parker: University of Manchester
Caroline Dive: Cancer Research UK Manchester Institute & Manchester Centre for Cancer Biomarker Sciences

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract Oncological use of anti-angiogenic VEGF inhibitors has been limited by the lack of informative biomarkers. Previously we reported circulating Tie2 as a vascular response biomarker for bevacizumab-treated ovarian cancer patients. Using advanced MRI and circulating biomarkers we have extended these findings in metastatic colorectal cancer (n = 70). Bevacizumab (10 mg/kg) was administered to elicit a biomarker response, followed by FOLFOX6-bevacizumab until disease progression. Bevacizumab induced a correlation between Tie2 and the tumor vascular imaging biomarker, Ktrans (R:−0.21 to 0.47) implying that Tie2 originated from the tumor vasculature. Tie2 trajectories were independently associated with pre-treatment tumor vascular characteristics, tumor response, progression free survival (HR for progression = 3.01, p = 0.00014; median PFS 248 vs. 348 days p = 0.0008) and the modeling of progressive disease (p

Date: 2018
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DOI: 10.1038/s41467-018-07174-1

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