Universität zu Köln

Goede, V., Coutelle, O., Neuneier, J., Reinacher-Schick, A., Schnell, R., Koslowsky, T. C., Weihrauch, M. R., Cremer, B., Kashkar, H., Odenthal, M., Augustin, H. G., Schmiegel, W., Hallek, M. and Hacker, U. T. (2010). Identification of serum angiopoietin-2 as a biomarker for clinical outcome of colorectal cancer patients treated with bevacizumab-containing therapy. Br. J. Cancer, 103 (9). S. 1407 - 1415. LONDON: NATURE PUBLISHING GROUP. ISSN 1532-1827

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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. British Journal of Cancer (2010) 103, 1407-1414. doi: 10.1038/sj.bjc.6605925 www.bjcancer.com Published online 5 October 2010 (C) 2010 Cancer Research UK

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Goede, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Coutelle, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Neuneier, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinacher-Schick, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schnell, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koslowsky, T. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Weihrauch, M. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cremer, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kashkar, H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Augustin, H. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmiegel, W. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hacker, U. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-494103
DOI:	10.1038/sj.bjc.6605925
Journal or Publication Title:	Br. J. Cancer
Volume:	103
Number:	9
Page Range:	S. 1407 - 1415
Date:	2010
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1532-1827
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TIE-2 LIGAND ANGIOPOIETIN-2; VASCULAR MORPHOGENESIS; ANGIOGENESIS; EXPRESSION; NORMALIZATION; ENDOTHELIUM; CARCINOMA; CETUXIMAB; ONCOLOGY; BENEFIT Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49410