%J Nature Communications
%K Tumour angiogenesis, Tumour biomarkers
%L discovery10074455
%V 9
%D 2018
%O © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
%T Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer
%X 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, K^{trans} (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 < 0.0001), suggesting that Tie2 should be monitored clinically to optimize VEGF inhibitor use. A vascular response is defined as a 30% reduction in Tie2; vascular progression as a 40% increase in Tie2 above the nadir. Tie2 is the first, validated, tumor vascular response biomarker for VEGFi.
%A GC Jayson
%A C Zhou
%A A Backen
%A L Horsley
%A K Marti-Marti
%A D Shaw
%A N Mescallado
%A A Clamp
%A MP Saunders
%A JW Valle
%A S Mullamitha
%A M Braun
%A J Hasan
%A D McEntee
%A K Simpson
%A RA Little
%A Y Watson
%A S Cheung
%A C Roberts
%A L Ashcroft
%A P Manoharan
%A SJ Scherer
%A O del Puerto
%A A Jackson
%A JPB O'Connor
%A GJM Parker
%A C Dive
%I NATURE PUBLISHING GROUP