AUA 2011 - Interleukin-6: A potential biomarker of resistance to multitargeted receptor tyrosine kinase inhibitors in castration-resistant prostate cancer - Session Highlights

WASHINGTON, DC USA ( - While tyrosine kinase inhibitors (TKIs) are undergoing testing in patients with castration-resistant prostate cancer (CRPC), there previously has been no biomarker to predict response.

These investigators importantly show that IL-6, known to be upregulated in CRPC, may predict response to TKIs. Previously, a heterogeneous response to sunitinib in Phase II trials has been noted. PSA levels were unreliable for prediction of response to TKIs. These researchers investigated whether cellular IL-6 production can predict TKI response in both an in-vitro and an in-vivo model. IL-6 mRNA levels were examined by RT-PCR. IL-6 protein expression was measured using ELISA, while apoptosis was examined using the TUNEL assay. For in-vivo studies, a CRPC xenograft model in C.B17/Icr-scid mice was employed.

CRPC cells exhibited heterogeneous responses to TKIs 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-alpha, IL-6 levels rose significantly upon administration of TKIs. These observations were confirmed in an in-vivo mouse model of CRPC.



Presented by Alexander Kutikov, et al. at the American Urological Association (AUA) Annual Meeting - May 14 - 19, 2011 - Walter E. Washington Convention Center, Washington, DC USA

Reported for UroToday by Christopher P. Evans, MD, FACS, Professor and Chairman, Department of Urology, University of California, Davis, School of Medicine.


The opinions expressed in this article are those of the Contributing Editor and do not necessarily reflect the viewpoints of the American Urological Association.



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