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

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.

Early Changes in Circulating FGF19 and Ang-2 Levels as Possible Predictive Biomarkers of Clinical Response to Lenvatinib Therapy in Hepatocellular Carcinoma

“…Ang-2 is known to be produced by cancer cells and plays important roles in regulating tumor angiogenesis [27,28,30]; additionally, it has been reported as a potential prognostic biomarker for certain types of cancers, including HCC [14,[24][25][26]. Several studies have reported high circulating (serum or plasma) Ang-2 levels as a predictor of tumor invasiveness or as a diagnostic biomarker of HCC [14,31,32].…”

A novel six-gene signature for prognosis prediction in ovarian cancer

“…For example, upregulated delta-like protein 3 (DLL3) overexpression is an independent prognostic predictor for endometrial cancer and could be a potential and novel tumor marker for the early diagnosis of endometrial cancer [10]. Plasma Tie2 is a tumor vascular response biomarker for vascular endothelial growth factor (VEGF) inhibitors in metastatic colorectal cancer [11]. Nevertheless, researchers found that rather than single gene biomarkers, gene signatures that include several genes can be good evidence for the prognosis and survival of tumors.…”

Dynamics of circulating vascular endothelial growth factor‐A predict benefit from antiangiogenic cediranib in metastatic or recurrent cervical cancer patients

“…The trajectory of VEGF‐R2, however, has not been investigated. We and others have reported on the clinical significance of angiopoietin pathway components (Ang1, Ang2 and Tie2) in patients receiving the VEGF inhibitor bevacizumab treatment for ovarian and colorectal cancer . On the basis of these previous studies, VEGF‐R2, VEGF‐A, Ang1 and Tie2 were selected for evaluation in this study.…”