- Renal cell carcinoma accounts for approximately 2.6% of all cancers in the United States1
- About 39,000 new cases of renal cell carcinoma are diagnosed every year and 13,000 Americans die annually from the disease1
- Currently, surgery (nephrectomy) is the only curative therapy for renal cell carcinoma. Estimated 5-year survival for patients whose disease is confined to the kidney is 90% to 95%2
- Approximately 33% of renal cell carcinoma patients present with metastatic disease2
- Patients with nonresectable or metastatic disease are primarily treated with cytokines (interleukin-2 [IL-2] or interferon alfa) or targeted therapies. Although IL-2 has been shown to achieve durable responses in a small number of stringently selected patients, treatment with cytokines or targeted therapies generally results in a median survival of 12 to 17.5 months and an estimated 5-year survival ranging from 0% to 20%2
- Hypoxia-inducible factor-1 (HIF-1) overexpression plays a key role in the pathogenesis of renal cell carcinoma3
- mTOR regulates HIF-1 expression by regulating production of HIF-α, an essential subunit of HIF-14,5 [Dysregulation of mTOR and several of its upstream effectors has been associated with abnormal HIF-1 expression in renal cell carcinoma6 In addition, up to 75% of patients with the clear-cell form of renal cell carcinoma have a defective von Hippel-Lindau (VHL) protein, which leads to HIF-α accumulation, also resulting in abnormally high levels of HIF-17
- Consequently, mTOR inhibition is considered a potentially promising therapeutic approach in renal cell carcinoma
- Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356(22):2271-2281.
- Mekhail TM, Abon-Jawde RM, BouMerhi G, et al. Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol. 2005;23(4):832-841.
- Pan J, Mestas J, Burdick MD, et al. Stromal derived factor-1 (SDF-1/CXCL12) and CXCR4 in renal cell carcinoma metastasis. Mol Cancer. 2006;5(1):56.
- Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov. 2006;5(8):671-688.
- Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 2003;3(10):721-732.
- Rathmell WK, Wright TM, Rini BI. Molecularly targeted therapy in renal cell carcinoma. Expert Rev Anticancer Ther. 2005;5(6):1031-1040.
- Patel PH, Chadalavada RSV, Chaganti RSK, Motzer RJ. Targeting the von Hippel-Lindau pathway in renal cell carcinoma. Clin Cancer Res. 2006;12(24):7215-7220.
References:
