%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