Abstract
The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically over the past few years. An improved understanding of the biology of RCC has resulted in the development of novel targeted therapeutic agents that have altered the natural history of this disease. In particular, the hypoxia-inducible factor (HIF)/vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) signal transduction pathway have been exploited. Sunitinib malate (Sutent), sorafenib tosylate (Nexavar), bevacizumab (Avastin)/interferon alfa, and temsirolimus (Torisel) have improved clinical outcomes in randomized trials by inhibiting these tumorigenic pathways. Combinations and sequences of these agents are being evaluated. Other novel multitargeted tyrosine kinase inhibitors (pazopanib and axitinib) and mTOR inhibitors (everolimus) are in clinical development. Recently reported and ongoing clinical trials will help further define the role of these agents as therapy for metastatic RCC.
MeSH terms
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Angiogenesis Inhibitors / therapeutic use*
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Antiviral Agents / therapeutic use
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Bevacizumab
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Carcinoma, Renal Cell / blood supply
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Carcinoma, Renal Cell / drug therapy
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Carcinoma, Renal Cell / secondary*
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Carcinoma, Renal Cell / therapy*
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Clinical Trials as Topic
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Disease-Free Survival
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
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Hypoxia-Inducible Factor 1, alpha Subunit / drug effects
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Immunologic Factors / therapeutic use
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Immunosuppressive Agents / therapeutic use
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Interleukin-2 / therapeutic use
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Kidney Neoplasms / blood supply
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Kidney Neoplasms / drug therapy
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Kidney Neoplasms / therapy*
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Pathologic / prevention & control
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Protein Kinase Inhibitors / therapeutic use*
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Protein Kinases
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Signal Transduction / drug effects
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TOR Serine-Threonine Kinases
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Treatment Outcome
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Vascular Endothelial Growth Factor A / antagonists & inhibitors
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Vascular Endothelial Growth Factor A / drug effects
Substances
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Angiogenesis Inhibitors
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Antiviral Agents
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Hypoxia-Inducible Factor 1, alpha Subunit
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Immunologic Factors
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Immunosuppressive Agents
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Interleukin-2
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Protein Kinase Inhibitors
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Vascular Endothelial Growth Factor A
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Bevacizumab
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Protein Kinases
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MTOR protein, human
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TOR Serine-Threonine Kinases