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Advanced renal-cell carcinoma is recognized as one of the most therapy-resistant epithelial neoplasms. In the early 1980s, work with the immune modulators interferon-α and interleukin-2 provided a glimmer of hope; however, except for a small subset of patients who benefit from interleukin-2, these toxic agents have not provided meaningful clinical benefit. Recent work has demonstrated that the von Hippel-Lindau tumor suppressor gene (VHL) is inactivated in most patients with clear-cell carcinoma, which is the most common histologic subtype of renal cancer. Inactivation of VHL ultimately results in increased expression of vascular endothelial growth factor (among others), thereby providing an important target for drug discovery.
Sorafenib is …