non renseigné

non renseigné

with the approval of bevacizumab (avastin ) for the treatment of advanced colon cancers, anti-angiogenesis has lately found entrance in adult oncology. however, final approval of an anti-angiogenic therapy for children with cancer is still missing. furthermore, several questions on the therapeutic concept of anti-angiogenesis are raised such as toxicity, combination with other drugs and biomarkers. our ongoing german-french collaboration has focused on the evaluation of different anti-angiogenic molecules such as tyrosinekinase inhibitors (tki), antibodies or angiogenesis targeting liposomes in pediatric solid tumor models. next to the proof on anti-tumor activity, the value of pharmacodynamic as well prognostic biomarkers is studied. we will explore three groups of biomarkers during anti-angiogenic therapy.1.) circulating endothelial cells (cecs) and circulating endothelial progenitor cells (ceps)- 2.) angiogenic factors isolated from thrombocytes and 3.) vascular imaging such as doppler contrast-enhanced ultrasound (dce-us) and dynamic contrast enhanced mri (dce-mri). the methodology to measure cecs and ceps by 4-colour flow cytometry in mouse and human whole blood has been established. quantification of vegf and bfgf can be realized after their liberation from thrombocytes by elisa. dce-us and dce-mri are available and ready to be evaluated during pre-clinical and clinical study protocols. the new tki for vegf-receptors ag-013736 (axitinib ) as well as liposomes harboring sirna directed against vegf will be studied in pediatric solid tumor animal models. furthermore, the biomarkers will be evaluated within two clinical phase ii studies of the anti-vegf. a antibody bevacizumab (avastin ) in combination with chemotherapy in children with high-risk and relapsing solid malignancies.