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

Author

Listed:
  • Gordon C. Jayson

    (University of Manchester)

  • Cong Zhou

    (University of Manchester)

  • Alison Backen

    (Cancer Research UK Manchester Institute & Manchester Centre for Cancer Biomarker Sciences)

  • Laura Horsley

    (University of Manchester)

  • Kalena Marti-Marti

    (University of Manchester)

  • Danielle Shaw

    (Clatterbridge Cancer Centre)

  • Nerissa Mescallado

    (University of Manchester)

  • Andrew Clamp

    (The Christie NHS Foundation Trust)

  • Mark P. Saunders

    (The Christie NHS Foundation Trust)

  • Juan W. Valle

    (University of Manchester)

  • Saifee Mullamitha

    (The Christie NHS Foundation Trust)

  • Mike Braun

    (The Christie NHS Foundation Trust)

  • Jurjees Hasan

    (The Christie NHS Foundation Trust)

  • Delyth McEntee

    (The Christie NHS Foundation Trust)

  • Kathryn Simpson

    (Cancer Research UK Manchester Institute & Manchester Centre for Cancer Biomarker Sciences)

  • Ross A. Little

    (University of Manchester)

  • Yvonne Watson

    (University of Manchester)

  • Susan Cheung

    (University of Manchester)

  • Caleb Roberts

    (University of Manchester)

  • Linda Ashcroft

    (The Christie NHS Foundation Trust)

  • Prakash Manoharan

    (University of Manchester)

  • Stefan J. Scherer

    (Novartis Pharmaceuticals Corporation)

  • Olivia Puerto

    (Del Puerto Limited)

  • Alan Jackson

    (University of Manchester)

  • James P. B. O’Connor

    (University of Manchester)

  • Geoff J. M. Parker

    (University of Manchester
    Bioxydyn Ltd)

  • Caroline Dive

    (Cancer Research UK Manchester Institute & Manchester Centre for Cancer Biomarker Sciences)

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

Suggested Citation

  • Gordon C. Jayson & Cong Zhou & Alison Backen & Laura Horsley & Kalena Marti-Marti & Danielle Shaw & Nerissa Mescallado & Andrew Clamp & Mark P. Saunders & Juan W. Valle & Saifee Mullamitha & Mike Brau, 2018. "Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07174-1
    DOI: 10.1038/s41467-018-07174-1
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