![]() ![]() Proliferative index, as defined by proliferating cell nuclear antigen or Ki-67 staining, has correlated with pathologic parameters and clinical outcomes in RCC, suggesting that regulation of the cell cycle plays an important role in the tumor biology of RCC ( Bui et al., 2004 Tollefson et al., 2007). Both of these mTOR inhibitors are now also approved by the FDA. Inhibition of mTOR with temsirolimus (Torisel) has yielded prolonged survival in patients with poor-risk, metastatic RCC, and everolimus (Afinitor) has shown efficacy for patients in whom tyrosine kinase inhibitors have failed, confirming the clinical relevance of the mTOR pathway (see Fig. Through complex pathways involving a variety of intermediaries, the mTOR pathway leads to increased expression of HIFs and other growth-promoting and potentially tumorigenic sequelae. Expression of mTOR is upregulated by various growth factors or by mutation or loss of PTEN. One such regulatory pathway in RCC is the mTOR pathway, which interfaces with Akt (protein kinase B) and the PTEN tumor suppressor gene ( Barthelemy et al., 2013 Hudes, 2009). Partin MD, PhD, in Campbell-Walsh-Wein Urology, 2021 Other Signal Transduction and Cell Cycle Regulation PathwaysĪberrant activation of additional signal transduction pathways in RCC may also contribute to altered cell cycle kinetics, and these pathways represent excellent targets for therapeutic intervention. ![]()
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