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

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    Authors
    Jayson, Gordon C
    Zhou, Cong
    Backen, Alison C
    Horsley, Laura
    Marti, Kalena
    Shaw, D
    Mescallado, Nerissa
    Clamp, Andrew R
    Saunders, Mark P
    Valle, Juan W
    Mullamitha, Saifee A
    Braun, Michael S
    Hasan, Jurjees
    McEntee, Delyth
    Simpson, Kathryn L
    Little, RA
    Watson, Y
    Cheung, S
    Roberts, C
    Ashcroft, Linda
    Manoharan, Prakash
    Scherer, SJ
    Del, PO
    Jackson, A
    O'Connor, James P B
    Parker, GJM
    Dive, Caroline
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    Affiliation
    The Christie NHS Foundation Trust and Division of Cancer Sciences, University of Manchester, Manchester, M20 4BX, UK
    Issue Date
    2018
    
    Metadata
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    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?<?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.
    Citation
    Jayson GC, Zhou C, Backen A, Horsley L, Marti-Marti K, Shaw D, et al. Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer. Nat Commun. 2018 Nov 7;9(1):4672.
    Journal
    Nature Communications
    URI
    http://hdl.handle.net/10541/621394
    DOI
    10.1038/s41467-018-07174-1
    Additional Links
    https://dx.doi.org/10.1038/s41467-018-07174-1
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-018-07174-1
    Scopus Count
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