%0 Journal Article
%@ 2041-1723
%A Jayson, GC
%A Zhou, C
%A Backen, A
%A Horsley, L
%A Marti-Marti, K
%A Shaw, D
%A Mescallado, N
%A Clamp, A
%A Saunders, MP
%A Valle, JW
%A Mullamitha, S
%A Braun, M
%A Hasan, J
%A McEntee, D
%A Simpson, K
%A Little, RA
%A Watson, Y
%A Cheung, S
%A Roberts, C
%A Ashcroft, L
%A Manoharan, P
%A Scherer, SJ
%A del Puerto, O
%A Jackson, A
%A O'Connor, JPB
%A Parker, GJM
%A Dive, C
%D 2018
%F discovery:10074455
%I NATURE PUBLISHING GROUP
%J Nature Communications
%K Tumour angiogenesis, Tumour biomarkers
%T Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer
%U https://discovery.ucl.ac.uk/id/eprint/10074455/
%V 9
%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.
%Z © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).