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172 |
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Practical Urology: EssEntial PrinciPlEs and PracticE |
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patients with the advanced form of the disease |
of renal cell carcinoma biology. That knowledge |
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(see Fig. 12.4). To date, there are a number of |
drove the development and testing of the tar- |
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compounds that are inhibitors of the mTOR |
geted therapies and their success in many ways |
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pathway and decrease HIFa, including rapamy- |
can be directly attributed to the work that shed |
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cin, temsirolimus, and everolimus (see also Cho |
light on that biology. This is an obvious and grat- |
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et al.,55 Boulay et al.,74 and Reddy et al.75). Of |
ifying example of science moving from bench to |
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these, the two that have received the greatest |
bedside and proof that an understanding of the |
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attention and have demonstrated efficacy in the |
biology of cancer can lead to tangible improve- |
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setting of advanced RCC are temsirolimus and |
ments in patient’s lives. As more such therapies |
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everolimus. Temsirolimus is a water-soluble |
are developed across a range of other diseases, it |
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ester of sirolimus,which is able to inhibit mTORs |
is clear that a fundamental understanding of |
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kinase activity, leading to cell cycle arrest. Phase |
molecular biology and its basic principles will be |
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II trials evaluating its efficacy both in combina- |
increasingly important in order to understand |
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tion with IFNa and as a single agent in cytokine |
how to manage our patients. |
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refractory advanced RCC suggested it improved |
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progression free survival when compared to his- |
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torical controls.76,77 These prompted a large- |
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