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Biomarkers for Anti-Angiogenic Therapy in Cancer
Clinic for Plastic, Aesthetic and Hand Surgery, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, Magdeburg D-39120, Germany
Max-Planck Institute for Biochemistry, Am Klopferspitz 18, Martinsried D-82152, Germany
Department of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Allé 4, 8000 Aarhus C, Denmark
Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Nørrebrogade 44, 8000 Aarhus C, Denmark
* Author to whom correspondence should be addressed.
Received: 28 February 2013; in revised form: 25 March 2013 / Accepted: 18 April 2013 / Published: 29 April 2013
Abstract: Angiogenesis, the development of new vessels from existing vasculature, plays a central role in tumor growth, survival, and progression. On the molecular level it is controlled by a number of pro- and anti-angiogenic cytokines, among which the vascular endothelial growth factors (VEGFs), together with their related VEGF-receptors, have an exceptional position. Therefore, the blockade of VEGF signaling in order to inhibit angiogenesis was deemed an attractive approach for cancer therapy and drugs interfering with the VEGF-ligands, the VEGF receptors, and the intracellular VEGF-mediated signal transduction were developed. Although promising in pre-clinical trials, VEGF-inhibition proved to be problematic in the clinical context. One major drawback was the generally high variability in patient response to anti-angiogenic drugs and the rapid development of therapy resistance, so that, in total, only moderate effects on progression-free and overall survival were observed. Biomarkers predicting the response to VEGF-inhibition might attenuate this problem and help to further individualize drug and dosage determination. Although up to now no definitive biomarker has been identified for this purpose, several candidates are currently under investigation. This review aims to give an overview of the recent developments in this field, focusing on the most prevalent tumor species.
Keywords: cancer; anti-angiogenic therapy; biomarkers; VEGF
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Wehland, M.; Bauer, J.; Magnusson, N.E.; Infanger, M.; Grimm, D. Biomarkers for Anti-Angiogenic Therapy in Cancer. Int. J. Mol. Sci. 2013, 14, 9338-9364.
Wehland M, Bauer J, Magnusson NE, Infanger M, Grimm D. Biomarkers for Anti-Angiogenic Therapy in Cancer. International Journal of Molecular Sciences. 2013; 14(5):9338-9364.
Wehland, Markus; Bauer, Johann; Magnusson, Nils E.; Infanger, Manfred; Grimm, Daniela. 2013. "Biomarkers for Anti-Angiogenic Therapy in Cancer." Int. J. Mol. Sci. 14, no. 5: 9338-9364.