Chapter 2 Signaling Pathways and Biomarkers in Renal Tumors

Sunitinib malate (Sutent, Pfizer inc., New York, NY) is an orally administered, multitargeted inhibitor of tyrosine kinases, including vascular endothelial growth factor (VEGF) receptor, platelet-derived growth factor (PDGF) receptor, stem cell factor receptor (KIT), fms-like ty‐ rosine kinase (FLT) -3, CSF-1R, and RET. Since the introduction of sunitinib for patients with advanced renal tumor [1], significant objective responses of sunitnib have been revealed [2-6]. In a randomized, multicenter, phase III trial enrolled 750 patients with previously-un‐ treated metastatic renal tumor to receive either sunitinib or interferon (IFN) -α, sunitinib was superior to IFN-α in the objective response rate (47% vs 12%), progression-free survival time (11.0 vs 5.0 months), and overall survival time (26.4 vs 21.8 months) [3, 4]. Also in a Jap‐ anese, multicenter, phase II trial enrolled 51 patients with first-line and pretreated metastatic clear-cell renal tumor to recieve sinitinib, significant responses of sunitinib have been report‐ ed that objective response rate was 52.9%, the median progression-free survival time was 12.2 and 10.6 months, and the median overall survival time was 33.1 and 32.5 months in first-line and pretreated patients, respectively [5, 6]. Sunitinib is approved worldwide for first-line treatment of advanced clear-cell renal tumor. However, approximately half of pa‐ tients with advanced renal tumor do not see clinical benefits from sunitinib treatment. A prognostic marker is needed for selecting patients who will benefit most from sunitinib.