408 INTERLEUKIN-6: A POTENTIAL BIOMARKER OF RESISTANCE TO MULTITARGETED RECEPTOR TYROSINE KINASE INHIBITORS IN CASTRATION-RESISTANT PROSTATE CANCER (2011)

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011408 INTERLEUKIN-6: A POTENTIAL BIOMARKER OF RESISTANCE TO MULTITARGETED RECEPTOR TYROSINE KINASE INHIBITORS IN CASTRATION-RESISTANT PROSTATE CANCER Alexander Kutikov, Peter Makhov, Konstantin Golovine, Daniel Canter, Mohit Sirohi, Ryan Street, Robert G. Uzzo, and Vladimir M. Kolenko Alexander KutikovAlexander Kutikov Philadelphia, PA More articles by this author , Peter MakhovPeter Makhov Philadelphia, PA More articles by this author , Konstantin GolovineKonstantin Golovine Philadelphia, PA More articles by this author , Daniel CanterDaniel Canter Philadelphia, PA More articles by this author , Mohit SirohiMohit Sirohi Philadelphia, PA More articles by this author , Ryan StreetRyan Street Philadelphia, PA More articles by this author , Robert G. UzzoRobert G. Uzzo Philadelphia, PA More articles by this author , and Vladimir M. KolenkoVladimir M. Kolenko Philadelphia, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.497AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Clinical experience using tyrosine kinase inhibitors (TKIs) in patients with castration-resistant prostate cancer (CRPC) is starting to mature. In Phase II trials, a heterogeneous response to sunitinib has been noted. PSA levels have proven unreliable for prediction of response to TKIs. IL-6 is a critical mediator of CRPC pathogenesis and has been shown to rise in patients with disease progression. As such, we investigated whether cellular IL-6 production can predict TKI response in both an in-vitro and an in-vivo model. METHODS IL-6 mRNA levels were examined by RT-PCR. IL-6 protein expression was investigated using ELISA, while apoptosis was examined using the TUNEL assay. For in-vivo studies CRPC xenograft model in C.B17/Icr-scid mice was employed. RESULTS CRPC cells exhibited heterogeneous response to sunitinib and pazopanib. Dose dependent reduction of IL-6 levels was observed in TKI-sensitive DU-145 cells. In contrast, the TKI-resistant PC-3 cells failed to suppress IL-6 excretion. Instead, in the presence of TNF-α, IL-6 levels rose significantly upon administration of TKIs. Findings of in-vitro experiments were confirmed in an in-vivo mouse model of CRPC. CONCLUSIONS Sensitivity of CRPC cells to TKIs is heterogeneous. These findings are consistent with results of recently-published Phase II clinical trials using sunitinib in patients with CRPC. A substantial rise in IL-6 levels occurs both in-vitro and in-vivo in the presence of TKIs in the resistant PC-3 cells but not in the TKI-sensitive DU-145 cells. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e165 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexander Kutikov Philadelphia, PA More articles by this author Peter Makhov Philadelphia, PA More articles by this author Konstantin Golovine Philadelphia, PA More articles by this author Daniel Canter Philadelphia, PA More articles by this author Mohit Sirohi Philadelphia, PA More articles by this author Ryan Street Philadelphia, PA More articles by this author Robert G. Uzzo Philadelphia, PA More articles by this author Vladimir M. Kolenko Philadelphia, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...