Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer.
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Date
2018-11-07ICR Author
Author
Jayson, GC
Zhou, C
Backen, A
Horsley, L
Marti-Marti, K
Shaw, D
Mescallado, N
Clamp, A
Saunders, MP
Valle, JW
Mullamitha, S
Braun, M
Hasan, J
McEntee, D
Simpson, K
Little, RA
Watson, Y
Cheung, S
Roberts, C
Ashcroft, L
Manoharan, P
Scherer, SJ
Del Puerto, O
Jackson, A
O'Connor, JPB
Parker, GJM
Dive, C
Type
Journal Article
Metadata
Show full item recordAbstract
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 < 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.
Collections
Subject
Humans
Colorectal Neoplasms
Disease Progression
Neovascularization, Pathologic
Receptor, TIE-2
Angiogenesis Inhibitors
Angiopoietin-2
Vascular Endothelial Growth Factor A
Prognosis
Disease-Free Survival
Models, Biological
Adult
Aged
Middle Aged
Female
Male
Kaplan-Meier Estimate
Biomarkers, Tumor
Bevacizumab
Research team
Quantitative Biomedical Imaging
Language
eng
Date accepted
2018-10-04
License start date
2018-11-07
Citation
Nature communications, 2018, 9 (1), pp. 4672 - ?
Publisher
NATURE PUBLISHING GROUP