WASHINGTON, DC USA (UroToday.com) - 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.