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; Meike Schneider

doi:10.18632/oncotarget.25697

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, Meike Schneider

Cancer Biology

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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.

Original language	English (US)
Pages (from-to)	30946-30961
Number of pages	16
Journal	Oncotarget
Volume	9
Issue number	57
DOIs	https://doi.org/10.18632/oncotarget.25697
State	Published - Jul 24 2018

Keywords

Bevacizumab
Damage associated molecular pattern
HMGB1
Renal cell carcinoma
VEGF

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.25697

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Schueler, J., Klingner, K., Bug, D., Zoeller, C., Maier, A., Dong, M., Willecke, K., Peille, A. L., Steiner, E., Landesfeind, M., Copland, J. A., Siegers, G. M., Haferkamp, A., Boehm, K., Tsaur, I., & Schneider, M. (2018). Patient derived renal cell carcinoma xenografts exhibit distinct sensitivity patterns in response to antiangiogenic therapy and constitute a suitable tool for biomarker development. Oncotarget, 9(57), 30946-30961. https://doi.org/10.18632/oncotarget.25697

Schueler, J, Klingner, K, Bug, D, Zoeller, C, Maier, A, Dong, M, Willecke, K, Peille, AL, Steiner, E, Landesfeind, M, Copland, JA, Siegers, GM, Haferkamp, A, Boehm, K, Tsaur, I & Schneider, M 2018, 'Patient derived renal cell carcinoma xenografts exhibit distinct sensitivity patterns in response to antiangiogenic therapy and constitute a suitable tool for biomarker development', Oncotarget, vol. 9, no. 57, pp. 30946-30961. https://doi.org/10.18632/oncotarget.25697

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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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AU - Schueler, Julia

AU - Klingner, Kerstin

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AU - Zoeller, Caren

AU - Maier, Armin

AU - Dong, Meng

AU - Willecke, Kerstin

AU - Peille, Anne Lise

AU - Steiner, Eva

AU - Landesfeind, Manuel

AU - Copland, John A.

AU - Siegers, Gabrielle M.

AU - Haferkamp, Axel

AU - Boehm, Katharina

AU - Tsaur, Igor

AU - Schneider, Meike

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N2 - 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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Patient derived renal cell carcinoma xenografts exhibit distinct sensitivity patterns in response to antiangiogenic therapy and constitute a suitable tool for biomarker development

Abstract

Keywords

ASJC Scopus subject areas

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