Publication:


abstract

bladder cancer patients who are refractory to chemotherapy have a poor prognosis. Furthermore, additional chemotherapies provide little benefit to patients who have relapsed after an initial response. Recently, it was reported that several molecular pathways are implicated in bladder carcinogenesis, including the epidermal growth factor receptor (EGFR) pathway, the vascular endothelial growth factor (VEGF) pathway and the Ras-MAPK pathway. We hypothesized that Sunitinib would be effective in bladder cancer as it is an oral inhibitor of multiple receptor tyrosine kinases, including VEGF receptors, platelet derived growth factor (PDGF) receptors and stem cell factor receptor (c-KIT), and is a standard first-line treatment of advanced clear cell renal carcinoma. In the present study, the antiproliferative effects of sunitinib were clearly demonstrated in KK47, KK47/DDP20 and KK47/ADR cell lines in vitro due to the suppression of ERK1/2 phosphorylation. In a mouse model, the antitumor effects of sunitinib were again clearly seen. Also, treatment with sunitinib decreased the abundance of regulatory T cells (Tregs). However, cytotoxic T lymphocyte (CTL) activity was not induced sufficiently as compared with an IFN-α-treated group. Our results suggested that sunitinib was effective in chemotherapy-resistant bladder cancer patients. On the other hand, these findings provided the rationale for combination therapy with sunitinib and immune-based cancer therapy for advanced malignancies to prevent the occurrence of rebound phenomena.

Related Articles
Review Sunitinib: a multitargeted receptor tyrosine kinase inhibitor in the era of molecular cancer therapies.
BioDrugs. 2009
Review Sunitinib: a multitargeted receptor tyrosine kinase inhibitor in the era of molecular cancer therapies.
Papaetis GS, Syrigos KN. BioDrugs. 2009; 23(6):377-89.
Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase.
Clin Cancer Res. 2003
Antitumor effects of ZD6474, a small molecule vascular endothelial growth factor receptor tyrosine kinase inhibitor, with additional activity against epidermal growth factor receptor tyrosine kinase.
Ciardiello F, Caputo R, Damiano V, Caputo R, Troiani T, Vitagliano D, Carlomagno F, Veneziani BM, Fontanini G, Bianco AR, et al. Clin Cancer Res. 2003 Apr; 9(4):1546-56.
Tyrosine kinase receptor inhibitor-targeted combined chemotherapy for metastatic bladder cancer.
Kaohsiung J Med Sci. 2012
Tyrosine kinase receptor inhibitor-targeted combined chemotherapy for metastatic bladder cancer.
Wu CL, Ping SY, Yu CP, Yu DS. Kaohsiung J Med Sci. 2012 Apr; 28(4):194-203. Epub 2011 Sep 25.
Sunitinib malate is active against human urothelial carcinoma and enhances the activity of cisplatin in a preclinical model.
Urol Oncol. 2009
Sunitinib malate is active against human urothelial carcinoma and enhances the activity of cisplatin in a preclinical model.
Sonpavde G, Jian W, Liu H, Wu MF, Shen SS, Lerner SP. Urol Oncol. 2009 Jul-Aug; 27(4):391-9. Epub 2008 Jun 4.
Review Sunitinib: from rational design to clinical efficacy.
J Clin Oncol. 2007
Review Sunitinib: from rational design to clinical efficacy.
Chow LQ, Eckhardt SG. J Clin Oncol. 2007 Mar 1; 25(7):884-96.