[HTML][HTML] Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy
V Goede, O Coutelle, J Neuneier… - British journal of …, 2010 - nature.com
V Goede, O Coutelle, J Neuneier, A Reinacher-Schick, R Schnell, TC Koslowsky…
British journal of cancer, 2010•nature.comBackground: The combination of chemotherapy with the vascular endothelial growth factor
(VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC).
However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking.
As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF,
we investigated its role as a biomarker in metastatic CRC. Methods: Serum Ang-2 levels
were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had …
(VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC).
However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking.
As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF,
we investigated its role as a biomarker in metastatic CRC. Methods: Serum Ang-2 levels
were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had …
Abstract
Background:
The combination of chemotherapy with the vascular endothelial growth factor (VEGF) antibody bevacizumab is a standard of care in advanced colorectal cancer (CRC). However, biomarkers predicting outcome of bevacizumab-containing treatment are lacking. As angiopoietin-2 (Ang-2) is a key regulator of vascular remodelling in concert with VEGF, we investigated its role as a biomarker in metastatic CRC.
Methods:
Serum Ang-2 levels were measured in 33 healthy volunteers and 90 patients with CRC. Of these, 34 had metastatic disease and received bevacizumab-containing therapy. To determine the tissue of origin of Ang-2, quantitative real-time PCR was performed on microdissected cryosections of human CRC and in a murine xenograft model of CRC using species-specific amplification.
Results:
Ang-2 originated from the stromal compartment of CRC tissues. Serum Ang-2 levels were significantly elevated in patients with metastatic CRC compared with healthy controls. Amongst patients receiving bevacizumab-containing treatment, low pre-therapeutic serum Ang-2 levels were associated with a significant better response rate (82 vs 31%; P< 0.01), a prolonged median progression-free survival (14.1 vs 8.5 months; P< 0.01) and a reduction of 91% in the hazard of death (P< 0.05).
Conclusion:
Serum Ang-2 is a candidate biomarker for outcome of patients with metastatic CRC treated with bevacizumab-containing therapy, and it should be further validated to customise combined chemotherapeutic and anti-angiogenic treatment.
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