Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer.
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
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
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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.
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
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
Description
Date
2018
Publisher
Collections
Keywords
Type
Article
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.