Role of mTOR in Renal Cell Carcinoma Development

Renal cell carcinoma (RCC) accounts for approximately 2.6% of all cancers in the United States.¹ About 39,000 new cases of RCC are diagnosed every year and 13,000 Americans die annually from the disease.¹

Deregulation of several signaling pathway components upstream from mTOR have been associated with RCC, including:

In addition, approximately 50% of patients with RCC have a defective von Hippel-Lindau (VHL) protein, which leads to HIF-1α accumulation and tumor angiogenesis.⁷

Currently, surgery (nephrectomy) is the only curative therapy for RCC. Estimated 5-year survival for patients whose disease is confined to the kidney is 90% to 95%.⁸ However, approximately one third of RCC patients present with metastatic disease. Patients with nonresectable or metastatic disease are primarily treated with biological or targeted therapies. Treatment with these agents results in a median survival of 12 to 17.5 months¹ and estimated 5-year survival ranges from 0% to 20%.⁸

Clearly, additional therapies for RCC are needed. Because of the involvement of TSC1/TSC2, Akt, PTEN, TGF, IGF-1/IGF-1R, and VHL in RCC, mTOR inhibitors are currently being investigated for the treatment of RCC. Several clinical trials have been completed, are underway, or are planned.

mTOR Clinical Trials

References:

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