Sunitinib enhances antitumor effects against chemotherapy-resistant bladder cancer through suppression of ERK1/2 phosphorylation

International Journal of Oncology
Ario TakeuchiSeiji Naito

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. Ou...Continue Reading

Citations

Oct 30, 2013·Molecular Medicine·Petros D GrivasMark L Day
Apr 25, 2014·BMC Cancer·Victoria MoneoAmancio Carnero
Dec 3, 2014·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Abhishek TripathiLauren C Harshman
Mar 5, 2013·Journal of Cancer Research and Clinical Oncology·D P ModestC J Bruns
Jan 10, 2014·Cancer Medicine·David F McDermott, Michael B Atkins
May 27, 2021·Cancer Biology & Therapy·Mohamed ElbadawyKazuaki Sasaki

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