TY - JOUR
T1 - Mammalian Target of Rapamycin Inhibitors in Renal Cell Carcinoma
T2 - Current Status and Future Applications
AU - Pantuck, Allan J.
AU - Thomas, George
AU - Belldegrun, Arie S.
AU - Figlin, Robert A.
PY - 2006/10
Y1 - 2006/10
N2 - Significant achievements in the basic sciences have led to a greater knowledge of the underlying signaling pathways in renal cell cancer (RCC), including the mammalian target of rapamycin (mTOR) pathway (phosphoinositide 3-kinase/Akt pathway). The mTOR pathway has a central role in the regulation of cell growth and increasing evidence suggests its dysregulation in cancer. Receiving input from multiple signals, including growth factors, hormones, nutrients, and other stimulants or mitogens, the pathway stimulates protein synthesis by phosphorylating key translation regulators such as ribosomal S6 kinase. The mTOR pathway also contributes to many other critical cellular functions, including protein degradation and angiogenesis. Hence, use of inhibitors of the pathway represents a new strategy for the targeted treatment of RCC, and mTOR inhibitors have already shown promising clinical efficacy and low toxicity profiles in unselected patients with metastatic RCC. As with other new, targeted cancer agents, the future use of mTOR inhibitors will benefit from reproducible biomarkers that can be used in the clinic to identify patients most likely to respond and to document modulation of the drug target in addition to clinical response.
AB - Significant achievements in the basic sciences have led to a greater knowledge of the underlying signaling pathways in renal cell cancer (RCC), including the mammalian target of rapamycin (mTOR) pathway (phosphoinositide 3-kinase/Akt pathway). The mTOR pathway has a central role in the regulation of cell growth and increasing evidence suggests its dysregulation in cancer. Receiving input from multiple signals, including growth factors, hormones, nutrients, and other stimulants or mitogens, the pathway stimulates protein synthesis by phosphorylating key translation regulators such as ribosomal S6 kinase. The mTOR pathway also contributes to many other critical cellular functions, including protein degradation and angiogenesis. Hence, use of inhibitors of the pathway represents a new strategy for the targeted treatment of RCC, and mTOR inhibitors have already shown promising clinical efficacy and low toxicity profiles in unselected patients with metastatic RCC. As with other new, targeted cancer agents, the future use of mTOR inhibitors will benefit from reproducible biomarkers that can be used in the clinic to identify patients most likely to respond and to document modulation of the drug target in addition to clinical response.
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U2 - 10.1053/j.seminoncol.2006.06.002
DO - 10.1053/j.seminoncol.2006.06.002
M3 - Article
C2 - 17045090
AN - SCOPUS:33749642343
SN - 0093-7754
VL - 33
SP - 607
EP - 613
JO - Seminars in Oncology
JF - Seminars in Oncology
IS - 5
ER -