Cediranib is a highly potent and selective
vascular endothelial growth factor (
VEGF) signaling inhibitor with activity against all three
VEGF receptors (VEGFRs) that inhibits angiogenesis and growth of human
tumor xenografts in vivo. The present study evaluated the antitumor and antiangiogenic activity of
cediranib in the clinically relevant, murine
renal cell carcinoma (RENCA) model and its
biological response using
VEGF and sVEGFR-2 as
biomarkers. Mice were treated with
cediranib (5 mg/kg/d p.o.) or vehicle for 2, 8 or 12 days and
tumor volumes, microvessel density (MVD) and
VEGF and sVEGFR-2 plasma concentrations were determined.
Cediranib treatment (8 and 12 days) led to a significant reduction in
tumor size (42-50%) and a highly significant reduction in MVD (30-55%) versus controls. After 12 days' treatment,
VEGF plasma concentration increased significantly in both
cediranib-treated and control animals and this increase correlated with
tumor size; the
cediranib group showed a more pronounced increase in
VEGF but a reduced
tumor volume compared with control animals. Plasma concentrations of
VEGF reached a plateau in the
cediranib group after 17-21 days' treatment. sVEGFR-2 concentrations significantly decreased over 12 days in controls, whereas they remained stable in
cediranib-treated mice. sVEGFR-2 did not correlate with
tumor volume in controls; mice treated with
cediranib had lower relative
VEGFR-2 plasma concentrations and
tumor burdens. In conclusion,
cediranib showed potent antitumor and antiangiogenic efficacy in the RENCA model. sVEGFR-2 plasma concentrations can act as a
surrogate marker for antitumor activity of VEGFR signaling inhibitors.