« Back Urologic Oncology: Seminars and Original Investigations

Article in Press

mTOR pathway inhibition in renal cell carcinoma

Received 28 September 2009 ,Revised 9 November 2009 ,Accepted 10 November 2009. Published online 08 March 2010 Corrected Proof

References 

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96
  2. Motzer RJ, Hutson T, Tomczak P, et al. Sunitinib vs. interferon α in metastatic renal-cell carcinoma. NEJM. 2007;356:115–124
  3. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. NEJM. 2007;356:125–134
  4. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon α-2a for treatment of metastatic renal-cell carcinoma: A randomised, double-blind phase III trial. Lancet. 2007;370:2103–2111
  5. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon α, or both, for advanced renal-cell carcinoma. NEJM. 2007;356:2271–2281
  6. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal-cell carcinoma: A randomized, double-blind, placebo-controlled phase III trial. Lancet. 2008;372:449–456
  7. Figlin RA. Mechanisms of disease: Survival benefit of temsirolimus validates a role for mTOR in the management of advanced RCC. Nat Clin Pract Oncol. 2008;5:601–609
  8. Inoki K, Corradetti MN, Guan KL. Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet. 2005;37:19–24
  9. Shaw RJ, Cantley LC. Ras, PI(3)K, and mTOR signaling controls tumor cell growth. Nature. 2006;441:424–430
  10. Dancey JE. Therapeutic targets: mTOR and related pathways. Cancer Biol Ther. 2006;5:1065–1073
  11. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007;12:9–22
  12. Kapoor A. Inhibition of mTOR in kidney cancer. Urol Oncol. 2009;16(S1):S33–S39
  13. Hudson CC, Liu M, Chiang GG, et al. Regulation of hypoxia-inducible factor 1-α expression and function by the mammalian target of rapamycin. Mol Cell Biol. 2002;22:7004–7014
  14. Abraham RT, Gibbons JJ. The mammalian target of rapamycin signaling pathway: Twists and turns in the road to cancer therapy. Clin Cancer Res. 2007;13:3109–3114
  15. Sarbassov DD, Guertin DA, Ali SM, et al. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307:1098–1101
  16. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7:606–619
  17. Patel PH, Chadalavada RS, Chaganti RS, et al. Targeting von Hippel-Lindau pathway in renal cell carcinoma. Clin Cancer Res. 2006;12:7215–7220
  18. Kapoor A, Figlin RA. Targeted inhibition of mammalian target of rapamycin for the treatment of advanced renal cell carcinoma. Cancer. 2009;115:3618–3630
  19. Brenner W, Farber G, Herget T, et al. Loss of tumor suppressor protein PTEN during renal carcinogenesis. Int J Cancer. 2002;99:53–57
  20. Robb VA, Karbowniczek M, Klein-Szanto AJ, et al. Activation of the mTOR signaling pathway in renal clear cell carcinoma. J Urol. 2007;177:346–352
  21. Pantuck AJ, Seligson DB, Klatte T, et al. Prognostic relevance of the mTOR pathway in renal cell carcinoma. Cancer. 2007;109:2257–2267
  22. Sehgal SN, Baker H, Vezina C. Rapamycin (AY22.989), a new antifungal antibiotic (II. Fermentation, isolation, and characterization). J Antibiot (Tokyo). 1975;28:727–732
  23. Helliwell SB, Wagner P, Kunz J, et al. TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. Mol Biol Cell. 1994;5:105–108
  24. Brown EJ, Albers MW, Shin TB, et al. A mammalian protein target by G1-arresting rapamycin-receptor complex. Nature. 1994;369:756–758
  25. Sabers CJ, Martin MM, Brunn GJ, et al. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J Biol Chem. 1995;270:815–822
  26. Dudkin L, Dilling M, Cheshire P, et al. Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition. Clin Cancer Res. 2001;7:1758–1764
  27. Yu K, Toral-Barza L, Discafani C, et al. mTOR, a novel target in breast cancer: The effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer. Endocr Relat Cancer. 2001;8:249–258
  28. Raymond E, Alexandre J, Faivre S, et al. Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer. J Clin Oncol. 2004;22:1–2
  29. Hidalgo M, Buckner JC, Erlichman C, et al. A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer. Clin Cancer Res. 2006;12:5755–5763
  30. Atkins MB, Hidalgo M, Stadler WM, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory cell carcinoma. J Clin Oncol. 2004;22:909–918
  31. Motzer RJ, Bacik J, Murphy BA, et al. Interferon-α as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol. 2002;20:289–296
  32. O'Donnell A, Faivre S, Burris HA, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol. 2008;26:1588–1595
  33. Tabernero J, Rojo F, Calvo E, et al. Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: A phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol. 2008;26:1603–1610
  34. Jac J, Giessinger S, Khan M, et al. A phase II trial of RAD001 in patients with metastatic renal cell carcinoma. J Clin Oncol. 2007;25(18 suppl):261s
  35. Amato RJ, Jac J, Giessinger S, et al. A phase II trial of RAD001 in patients with metastatic renal cell carcinoma. Cancer. 2009;115:2438–2446
  36. Merchan JR, Pitot HC, Qin R, et al. Phase I/II trial of CCI-779 and bevacizumab in advanced renal cell carcinoma (RCC): Safety and activity in RTKI refractory patients. J Clin Oncol 20;27(Suppl):15s [Abstract 5039].
  37. Patnaik A, Ricart A, Cooper J, et al. A phase I, pharmacokinetic and pharmacodynamic study of sorafenib, a multitargeted kinase inhibitor in combination with temsirolimus, an mTOR inhibitor, in patients with advanced solid malignancies. Proc Am Soc Clin Oncol. 2007;25(Suppl):141s;[Abstract 3512].
  38. Patel PH, Senico PL, Curiel RE, et al. Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma. Clin Genitourin Cancer. 2009;7:24–27
  39. Neshat MS, Mellinghoff IK, Tran C, et al. Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. PNAS. 2001;98:10314–10319
  40. Rini BI, Atkins MB. Resistance to targeted therapy in renal cell carcinoma. Lancet Oncol. 2009;10:992–1000

PII: S1078-1439(09)00361-5

doi: 10.1016/j.urolonc.2009.11.008

« Back Urologic Oncology: Seminars and Original Investigations

Article in Press