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Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Jilaveanu, LB and Zhao, F and Zito, CR and Kirkwood, JM and Nathanson, KL and D'Andrea, K and Wilson, M and Rimm, DL and Flaherty, KT and Lee, SJ and Kluger, HM (2013) Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel. PLoS ONE, 8 (8).

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Abstract

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Jilaveanu, LB
Zhao, F
Zito, CR
Kirkwood, JMkirkwood@pitt.eduKIRKWOOD
Nathanson, KL
D'Andrea, K
Wilson, M
Rimm, DL
Flaherty, KT
Lee, SJ
Kluger, HM
Centers: Other Centers, Institutes, Offices, or Units > Hillman Cancer Center
Date: 6 August 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0069748
Refereed: Yes
Date Deposited: 23 Sep 2013 17:52
Last Modified: 19 Feb 2019 05:55
URI: http://d-scholarship.pitt.edu/id/eprint/19782

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