Patient derived renal cell carcinoma xenografts exhibit distinct sensitivity patterns in response to antiangiogenic
Julia Schueler1, Kerstin Klingner1, Daniel Bug2
1Charles River Discovery Research Services Germany GmbH, Freiburg, Germany.
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.
Insights
High mobility group B1 (HMGB1) protein levels in serum can predict treatment response in renal cell carcinoma. Elevated HMGB1 indicates potential sensitivity to bevacizumab therapy, aiding personalized treatment strategies.
Area of Science:
- Oncology
- Biomarker Discovery
- Translational Research
Background:
- Renal cell carcinoma (RCC) often requires systemic treatment, but lacks predictive biomarkers for personalized therapy.
- Current treatment selection for RCC is not optimized due to the absence of reliable predictive markers.
Purpose of the Study:
- To investigate high mobility group B1 (HMGB1) as a predictive biomarker for systemic therapy response in renal cell carcinoma.
- To evaluate serum HMGB1 levels in patient-derived xenograft (PDX) models of RCC treated with various systemic agents.
Main Methods:
- Established a panel of RCC patient-derived xenograft (PDX) mouse models.
- Measured serum HMGB1 levels in PDX models during treatment with sunitinib, pazopanib, sorafenib, axitinib, temsirolimus, and bevacizumab.
- Correlated pre-treatment serum HMGB1 levels with tumor growth and treatment response.
Main Results:
- Serum HMGB1 levels were significantly higher in a subset of PDX models with slower tumor growth.
- Pre-treatment serum HMGB1 levels correlated with response to systemic treatments.
- High serum HMGB1 levels predicted response to bevacizumab in RCC PDX models.
Conclusions:
- High mobility group B1 (HMGB1) shows potential as a predictive biomarker for bevacizumab sensitivity in renal cell carcinoma.
- HMGB1 may help tailor systemic therapy selection for RCC patients.
- Further clinical evaluation of HMGB1 for predicting bevacizumab response is warranted.
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