%0 Journal Article %1 Ebos.2007 %A Ebos, J. M. %A Lee, C. R. %A Christensen, J. G. %A Mutsaers, A. J. %A Kerbel, R. S. %D 2007 %J Proc.Natl.Acad.Sci.U.S.A %K & A Administration Agents Angiogenesis Animals Antineoplastic Antitumor Assays Blood Cell Dose-Response Drug Endothelial Factor Female Growth Humans Hypoxia Indoles Inducing Line Mice Model Neoplasms Organ Outcome Placenta Pregnancy Proteins Pyrroles RANGE Receptor-2 Relationship Research Schedule Scid Specificity Treatment Tumor Tyrosine Vascular Xenograft administration blood dosage drug effects metabolism pathology pharmacology protein response therapy toxicity %N 43 %P 17069-17074 %T Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy %U PM:17942672 %V 104 %X Cancer patients treated with antiangiogenic multitargeted receptor tyrosine kinase (RTK) inhibitors show increased levels of plasma VEGF and placental growth factor and decreased levels of soluble VEGF receptor-2, thus implicating these overall changes as a possible class effect of such drugs and raising the possibility of their exploitation as surrogate biomarkers for pharmacodynamic drug activity/exposure and patient benefit. A postulated mechanism for these changes is that they are tumor-dependent, resulting from drug-induced decreases in vascular function, increases in tumor hypoxia, and changes in hypoxia-regulated genes. However, here we report that an identical pattern of change is observed in normal nontumor-bearing mice treated with SU11248/sunitinib, a small-molecule inhibitor of VEGF and PDGF RTKs. The changes were dose-dependent, plateaued after 4 days of consecutive treatment, reversed after discontinuation of therapy, and correlated with antitumor activity. Altered protei

@article{Ebos.2007, abstract = {Cancer patients treated with antiangiogenic multitargeted receptor tyrosine kinase (RTK) inhibitors show increased levels of plasma VEGF and placental growth factor and decreased levels of soluble VEGF receptor-2, thus implicating these overall changes as a possible class effect of such drugs and raising the possibility of their exploitation as surrogate biomarkers for pharmacodynamic drug activity/exposure and patient benefit. A postulated mechanism for these changes is that they are tumor-dependent, resulting from drug-induced decreases in vascular function, increases in tumor hypoxia, and changes in hypoxia-regulated genes. However, here we report that an identical pattern of change is observed in normal nontumor-bearing mice treated with SU11248/sunitinib, a small-molecule inhibitor of VEGF and PDGF RTKs. The changes were dose-dependent, plateaued after 4 days of consecutive treatment, reversed after discontinuation of therapy, and correlated with antitumor activity. Altered protei}, added-at = {2010-02-05T11:28:39.000+0100}, author = {Ebos, J. M. and Lee, C. R. and Christensen, J. G. and Mutsaers, A. J. and Kerbel, R. S.}, biburl = {https://www.bibsonomy.org/bibtex/2ef0f98aaa58251a4ab8b2c0be419ef9e/kanefendt}, interhash = {f3ae59b27c9d7892da72bfc272b9d02b}, intrahash = {ef0f98aaa58251a4ab8b2c0be419ef9e}, journal = {Proc.Natl.Acad.Sci.U.S.A}, keywords = {& A Administration Agents Angiogenesis Animals Antineoplastic Antitumor Assays Blood Cell Dose-Response Drug Endothelial Factor Female Growth Humans Hypoxia Indoles Inducing Line Mice Model Neoplasms Organ Outcome Placenta Pregnancy Proteins Pyrroles RANGE Receptor-2 Relationship Research Schedule Scid Specificity Treatment Tumor Tyrosine Vascular Xenograft administration blood dosage drug effects metabolism pathology pharmacology protein response therapy toxicity}, number = 43, pages = {17069-17074}, timestamp = {2010-02-05T11:28:55.000+0100}, title = {Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy}, url = {PM:17942672}, volume = 104, year = 2007 }