Sorafenib Acts through VEGFR-2 Inhibition in a Metastatic Clear-Cell Sarcoma of the Kidney

Abstract

We report here the case of a young patient with metastatic clear-cell sarcoma of the kidney resistant to standard chemotherapy, and with complete response under sorafenib treatment. The remarkable response of her tumor to sorafenib led us to study sorafenib molecular targets in the metastatic tissue. Background: Biomarkers predicting response to anti-angiogenic tyrosine kinase inhibitors remain to be identified. Methods and Findings: In this paper, we studied the molecular targets of sorafenib in the lung metastasis of a kidney clear-cell sarcoma. In a patient with complete response under sorafenib treatment, we showed high VEGFR2 expression by tumor endothelial cells from the lung metastasis. Conclusion: The original mechanistic results that we obtained using immunostainings and quantitative RT-PCR on laser-microdissected tumor endothelial cells have a direct application in daily clinical practice: metastatic tumors with a large angiogenic component should be tested for VEGFRs expression to consider anti-angiogenic tyrosine kinase inhibitor treatments.