Jayson, GC;
Zhou, C;
Backen, A;
Horsley, L;
Marti-Marti, K;
Shaw, D;
Mescallado, N;
... Dive, C; + view all
(2018)
Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer.
Nature Communications
, 9
, Article 4672. 10.1038/s41467-018-07174-1.
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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, 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.
| Type: | Article |
|---|---|
| Title: | Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-018-07174-1 |
| Publisher version: | https://doi.org/10.1038/s41467-018-07174-1 |
| Language: | English |
| Additional information: | © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Tumour angiogenesis, Tumour biomarkers |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10074455 |
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