Abstract
Researchers have recently demonstrated a significant activity in the use of antiangiogenic compounds for the treatment of clear-cell metastatic renal cell carcinoma (RCC). The pVHL protein plays an important role in angiogenesis. Germline or somatic alterations of the VHL gene result in an abnormal accumulation of hypoxia inducible factor (HIF) inducing the upregulation of proangiogenic downstream genes. From a cohort of 13 patients with RCC included in a phase II study testing the activity of AG-013736 (axitinib), a multi-target receptor tyrosine kinase inhibitor (including VEGFR-1 and -2, PDGFR-β), we investigated the correlation between the presence of VHL somatic mutations and the activity of axitinib. Tumor samples collected were formalin-fixed paraffin-embedded tissues. DNA extracted from these samples were PCR-amplified and directly sequenced for the VHL gene. Among the 13 tumor DNA samples studied, 12 were successfully sequenced. There was an objective response in six patients. Two patients who experienced an objective response had evidence of VHL sequence variants. No VHL mutation was detected among the other patients. In conclusion, no correlation was observed between the somatic mutational status of the VHL gene and the objective response to axitinib in our series.
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Acknowledgements
This work was supported in part by grants from the Ligue Nationale contre le Cancer (Comité du Cher et de l’Indre) and INCa (Institut National du Cancer, PNES). We thank Dr. Francis Cajfinger for expert assistance in preparation of this manuscript.
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Gad, S., Sultan-Amar, V., Meric, JB. et al. Somatic von Hippel-Lindau (VHL) gene analysis and clinical outcome under antiangiogenic treatment in metastatic renal cell carcinoma: preliminary results. Targ Oncol 2, 3–6 (2007). https://doi.org/10.1007/s11523-006-0039-9
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DOI: https://doi.org/10.1007/s11523-006-0039-9