Oncotarget

Research Papers:

Patient derived renal cell carcinoma xenografts exhibit distinct sensitivity patterns in response to antiangiogenic therapy and constitute a suitable tool for biomarker development

Julia Schueler, Kerstin Klingner, Daniel Bug, Caren Zoeller, Armin Maier, Meng Dong, Kerstin Willecke, Anne-Lise Peille, Eva Steiner, Manuel Landesfeind, John A. Copland, Gabrielle M. Siegers, Axel Haferkamp, Katharina Boehm, Igor Tsaur and Meike Schneider _

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Oncotarget. 2018; 9:30946-30961. https://doi.org/10.18632/oncotarget.25697

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Abstract

Julia Schueler1, Kerstin Klingner1, Daniel Bug3, Caren Zoeller7, Armin Maier1, Meng Dong8, Kerstin Willecke8, Anne-Lise Peille1, Eva Steiner4, Manuel Landesfeind1, John A. Copland2, Gabrielle M. Siegers6, Axel Haferkamp5, Katharina Boehm5, Igor Tsaur5 and Meike Schneider5

1Charles River Discovery Research Services Germany GmbH, Freiburg, Germany

2Department of Cancer Biology, Mayo Clinic, Jacksonville, FL, USA

3LfB – Lehrstuhl für Bildverarbeitung, RWTH Aachen University, Aachen, Germany

4Department of Urology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany

5Department of Urology, Medical Center Johannes Gutenberg University, Mainz, Germany

6Department of Experimental Oncology, University of Alberta, 5-142W Katz Group Centre, Edmonton, Canada

7Department of Radiation Oncology, University Hospital of Würzburg, Würzburg, Germany

8Dr. Margarete Fischer-Bosch - Institut für Klinische Pharmakologie, Stuttgart, Germany

Correspondence to:

Meike Schneider, email: meikeschneider310@gmail.com

Keywords: HMGB1; renal cell carcinoma; damage associated molecular pattern; bevacizumab; VEGF

Received: November 11, 2017    Accepted: June 12, 2018    Published: July 24, 2018

ABSTRACT

Systemic treatment is necessary for one third of patients with renal cell carcinoma. No valid biomarker is currently available to tailor personalized therapy. In this study we established a representative panel of patient derived xenograft (PDX) mouse models from patients with renal cell carcinomas and determined serum levels of high mobility group B1 (HMGB1) protein under treatment with sunitinib, pazopanib, sorafenib, axitinib, temsirolimus and bevacizumab. Serum HMGB1 levels were significantly higher in a subset of the PDX collection, which exhibited slower tumor growth during subsequent passages than tumors with low HMGB1 serum levels. Pre-treatment PDX serum HMGB1 levels also correlated with response to systemic treatment: PDX models with high HMGB1 levels predicted response to bevacizumab. Taken together, we provide for the first time evidence that the damage associated molecular pattern biomarker HMGB1 can predict response to systemic treatment with bevacizumab. Our data support the future evaluation of HMGB1 as a predictive biomarker for bevacizumab sensitivity in patients with renal cell carcinoma.


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