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Jayson, Gordon C; Zhou, Cong; Backen, Alison; Horsley, Laura; Marti-Marti, Kalena; Shaw, Danielle; Mescallado, Nerissa; Clamp, Andrew; Saunders, Mark P; Valle, Juan W; Mullamitha, Saifee; Braun, Mike; Hasan, Jurjees; McEntee, Delyth; Simpson, Kathryn; Little, Ross A; Watson, Yvonne; Cheung, Susan; Roberts, Caleb; Ashcroft, Linda; Manoharan, Prakash; Scherer, Stefan J; Del Puerto, Olivia; Jackson, Alan; O'Connor, James P B; Parker, Geoff J M; Dive, Caroline
Nature communications, 11/2018, Volume: 9, Issue: 1Journal Article
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 (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.
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