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

  • 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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Author:Julia Schüler, Kerstin Klingner, Daniel Bug, Caren Zöller, Armin Maier, Meng Dong, Kerstin Willecke, Anne-Lise Peille, Eva Steiner, Manuel Landesfeind, John A. Copland, Gabrielle M. Siegers, Axel Haferkamp, Katharina Böhm, Igor TsaurORCiDGND, Meike Schneider
URN:urn:nbn:de:hebis:30:3-465395
DOI:https://doi.org/10.18632/oncotarget.25697
ISSN:1949-2553
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/30123419
Parent Title (English):OncoTarget
Publisher:Impact Journals LLC
Place of publication:[s. l.]
Document Type:Article
Language:English
Year of Completion:2018
Date of first Publication:2018/07/24
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2018/08/30
Tag:HMGB1; VEGF; bevacizumab; damage associated molecular pattern; renal cell carcinoma
Volume:9
Issue:57
Page Number:16
First Page:30946
Last Page:30961
Note:
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
HeBIS-PPN:45064412X
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0