Patient derived renal cell carcinoma xenografts exhibit distinct sensitivity patterns in response to antiangiogenic therapy and constitute a suitable tool for biomarker development
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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
Meike Schneider, email: firstname.lastname@example.org
Keywords: HMGB1; renal cell carcinoma; damage associated molecular pattern; bevacizumab; VEGF
Received: November 11, 2017 Accepted: June 12, 2018 Published: July 24, 2018
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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