Therapeutic rationale for mTOR inhibition in advanced renal cell carcinoma

Current Clinical Pharmacology

Volumn 6, Issue 3, 2011, Pages 214-221

  Husseinzadeh, Holleh D ^a   Garcia, Jorge A ^b  

^a Medicine Institute   (United States)

^b TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

Everolimus; Mammalian target of rapamycin (mTOR); Renal cell carcinoma (RCC); Temsirolimus

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; ALPHA INTERFERON; BEVACIZUMAB; DEFEROLIMUS; EVEROLIMUS; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; RAPAMYCIN; SORAFENIB; SUNITINIB; TEMSIROLIMUS; UNCLASSIFIED DRUG; VASCULOTROPIN INHIBITOR;

ADVANCED CANCER; ANEMIA; ANOREXIA; ANTIANGIOGENIC ACTIVITY; ARTICLE; ASTHENIA; BINDING AFFINITY; BIPOLAR DISORDER; CANCER GROWTH; CANCER INHIBITION; CANCER RISK; CANCER SURVIVAL; CELL PROLIFERATION; CELLULITIS; CREATININE BLOOD LEVEL; DIARRHEA; DRUG ACTIVITY; DRUG BINDING; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG METABOLISM; DRUG SAFETY; DRUG STABILITY; DRUG STRUCTURE; DRUG TARGETING; DRUG TOLERABILITY; DRUG WITHDRAWAL; FATIGUE; HUMAN; KIDNEY CARCINOMA; LUNG EMBOLISM; MACULOPAPULAR RASH; MITOSIS INHIBITION; MUCOSA INFLAMMATION; NAUSEA; NEUTROPENIA; OVERALL SURVIVAL; PNEUMONIA; PRIORITY JOURNAL; PROTEINURIA; RASH; SIDE EFFECT; STOMATITIS; THROMBOCYTOPENIA; TUMOR VOLUME; VOMITING;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, RENAL CELL; CLINICAL TRIALS AS TOPIC; HUMANS; KIDNEY NEOPLASMS; TOR SERINE-THREONINE KINASES;

EID: 80052207596     PISSN: 15748847     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488411797189433     Document Type: Article

References (81)

1. Rini BI, Small EJ. Biology and clinical development of vascular endothelial growth factor-targeted therapy in renal cell carcinoma. J lin Oncol 2005; 23: 1028-43
2. Motzer RJ, Bukowski RM. Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol 2006; 24: 5601-8
3. Garcia JA, Rini BI. Recent progress in the management of advanced renal cell carcinoma. CA Cancer J Clin 2007; 57: 112-25
4. Presta LG, Chen H, O'Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 1997; 57: 4593-9
5. Rini BI, Halabi S, Rosenberg JE, et al. Phase III trial of bevacizu-mab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol 2010; 28: 2137-43
6. Escudier B, Bellmunt J, Negier S. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carci-noma (AVOREN): final analysis of overall survival. J Clin Oncol 2010; 28: 2144-50
7. Motzer RJ, Hutson TE, Tomczack P, et al. Sunitinib versus inter-feron alfa in metastatic renal-cell carcinoma. N Engl J Med 2007; 356: 115-24
8. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125-34. Erratum in: N Engl J Med 2007; 357: 203
9. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010; 28: 1061-8
10. Borders EB, Bivona C, Medina PJ. Mammalian target of rapamycin: biological function and target for novel anticancer agents. Am J Health Syst Pharm 2010; 67: 2095-106
11. Sánchez R, Espinosa A, Zamora A, et al. mTOR pathway inhibition in renal cell carcinoma. Pinto Marín A, Urol Oncol 2010
12. Kapoor A, Figlin RA. Targeted inhibition of mammalian target of rapamycin for the treatment of advanced renal cell carcinoma. Cancer 2009; 115: 3618-30
13. Cho D, Signoretti S, Regan M, Mier JW, Atkins MB. The role of mammalian target of rapamycin inhibitors in the treatment of advanced renal cancer. Clin Cancer Res 2007; 13: 758s-63s
14. Dasanu CA, Clark BA 3rd, Alexandrescu DT. mTOR-blocking agents in advanced renal cancer: an emerging therapeutic option. Expert Opin Investig Drugs 2009; 2: 175-87
15. Wysocki PJ. mTOR in renal cell cancer: modulator of tumor biology and therapeutic target. Expert Rev Mol Diagn 2009; 3: 231-41. http://www.ncbi.nlm.nih.gov/pubmed/19442061
16. Konings IR, Verweij J, Wiemer EA, Sleijfer S. The applicability of mTOR inhibition in solid tumors. Curr Cancer Drug Targets 2009; 3: 439-50
17. Hudes GR. Targeting mTOR in renal cell carcinoma. Cancer 2009; 115: 2313-20
18. Pantuck AJ, Thomas G, Belldegrun AS, Figlin RA. Mammalian target of rapamycin inhibitors in renal cell carcinoma: current status and future applications. Semin Oncol 2006; 33: 607-13
19. Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 2009; 10: 307-18
20. Schmelzle T, Hall MN. TOR, a central controller of cell growth. Cell 2000; 103: 253-62
21. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 2007; 12: 9-22
22. Dufner A, Thomas G. Ribosomal S6 kinase signaling and the control of translation. Exp Cell Res 1999; 253: 100-9
23. Kim DH, Sabatini DM. Raptor and mTOR: subunits of a nutrient-sensitive complex. Curr Top Microbiol Immunol 2004; 279: 259-70
24. Kim JE, Chen J. Regulation of peroxisome proliferatoractivated receptor-gamma activity by mammalian target of rapamycin and amino acids in adipogenesis. Diabetes 2004; 53: 2748-56
25. Huffman TA, Mothe-Satney I, Lawrence JC Jr. Insulinstimulated phosphorylation of lipin mediated by the mammalian target of rapamycin. Proc Natl Acad Sci USA 2002; 99: 1047-52
26. Reue K, Zhang P. The lipin protein family: dual roles in lipid bio-synthesis and gene expression. FEBS Lett 2008; 582: 90-96
27. Fingar DC, Blenis J. Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 2004; 23: 3151-71
28. Kimball SR. Interaction between the AMP-activated protein kinase and mTOR signaling pathways. Med Sci Sports Exerc 2006; 38: 1958-64
29. Hudson CC, Liu M, Chiang GG, et al. Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol 2002; 22: 7004-14
30. Zhong H, Chiles K, Feldser D, et al. Modulation of hypoxia-inducible factor 1-alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/ PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 2000; 60: 1541-5
31. Garcia JA, Danielpour D. Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malig-nancies. Mol Cancer Ther 2008; 6: 1347-54
32. Kim DH, Sarbassov DD, Ali SM, et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 2002; 110: 163-75
33. Hara K, Maruki Y, Long X, et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 2002; 110: 177-89
34. Jacinto E, Facchinetti V, Liu D, et al. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 2006; 127: 125-37
35. Li J, Yen C, Liaw D, et al. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997; 275: 1943-7
36. Teng DH, Hu R, Lin H, et al. MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines. Cancer Res 1997; 57: 5221-5
37. El-Hashemite N, Walker V, Zhang H, Kwiatkowski DJ. Loss of Tsc1orTsc2 induces vascular endothelial growth factor production through mammalian target of rapamycin. Cancer Res 2003; 63: 5173-7
38. Brugarolas JB, Vazquez F, Reddy A, Sellers WR, Kaelin WG. TSC2 regulates VEGF through mTORdependent and -independent pathways. Cancer Cell 2003; 4: 147-58
39. Robb VA, Karbowniczek M, Klein-Szanto AJ, et al. Activation of the mTOR signaling pathway in renal clear cell carcinoma. J Urol 2007; 177: 346-52
40. Pantuck AJ, Seligson DB, Klatte T, et al. Prognostic relevance of the mTOR pathway in renal cell carcinoma. Cancer 2007; 109: 2257-67
41. Cho D, Signoretti S, Regan M, et al. The role of mammalian target of rapamycin inhibitors in the treatment of advanced renal cancer. Clin Cancer Res 2007; 13: 758s-63s
42. Iliopoulos O, Kibel A, Gray S, KaelinWG, Jr. Tumour suppression by the human von Hippel-Lindau gene product. NatMed 1995; 1: 822-826
43. de Paulsen N, Brychzy A, Fournier, et al. Role of transforming growth factor-a in von Hippel-Lindau (VHL) (_/_) clear cell renal carcinoma cell proliferation: a possible mechanism coupling VHL tumor suppressor inactivation and tumorigenesis. Proc Natl Acad Sci USA 2000; 98: 1387-92
44. Laughner E, Taghavi P, Chiles K, Mahon PC, Semenza GL. HER2 (neu) signaling increases rate of hypoxia-inducible factor 1a (HIF-1a) synthesis: novel mechanism for HIF-1mediated vascular endothelial growth factor expression. Mol Cell Biol 2001; 21: 3995-4004
45. Thomas GV, Tran C, Mellinghoff IK, et al. Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. NatMed 2006; 12: 122-7
46. 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: 2336-47
47. 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 renal cell carcinoma. J Clin Oncol 2004; 22: 909-18
48. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 2007; 356: 2271-81
49. Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M. Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 2002; 20: 289-96
50. Mekhail TM, Abou-Jawde RM, Boumerhi G, et al. Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 2005; 23: 832-41
51. Motzer RJ, Hudes GR, Curti BD, et al. Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma. J Clin Oncol 2007; 25: 3958-64
52. Bellmunt J, Szczylik C, Feingold J, et al. Temsirolimus safety profile and management of toxic effects in patients with advanced renal cell carcinoma and poor prognostic features. Ann Oncol 2008; 19: 1387-92
53. Duran I, Siu LL, Oza AM, et al. Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus. Eur J Cancer 2006; 42: 1875-80
54. Galanis E, Buckner JC, Maurer MJ, et al. Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: A North Central Cancer Treatment Group Study. J Clin Oncol 2005; 23: 5294-304
55. Witzig TE, Geyer SM, Ghobrial I, et al. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 2005; 23: 5347-56
56. Maroto JP, Hudes G, Dutcher JP, et al. Drug-related pneumonitis in patients with advanced renal cell carcinoma treated with temsirolimus. J Clin Oncol 2011; 29: 1750-6
57. Dutcher JP, de Souza P, McDermott D, et al. Effect of temsirolimus versus interferon-alpha on outcome of patients with advanced renal cell carcinoma of different tumor histologies. Med Oncol 2009; 26: 202-9
58. http://www.ncbi.nlm.nih.gov/pubmed/19526589Figlin RA, de Souza P, McDermott D, et al. Analysis of PTEN and HIF-1alpha and correlation with efficacy in patients with advanced renal cell carcinoma treated with temsirolimus versus interferon-alpha Cancer 2009; 115: 3651-60
59. Pascual J, Boletis IN, Campistol JM. Everolimus (Cerican) in renal transplantation: A review of clinical trial data, current usage, and future directions. Transplant Rev 2006; 20: 1-18
60. Eisen HJ, Tuzcu M, Dorent R, et al. Everolimus for the prevention of allograft rejection and vaculopathy in cardiac-transplant patients. N Engl J Med 2003; 349: 847-58
61. O'Donnell A, Faivre S, Burris HA 3rd, 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: 1588-95
62. Amato RJ, Jac J, Giessinger S, et al. A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (Everolimus) in patients with metastatic clear cell renal cancer. Cancer 2009; 115: 2438-46
63. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of Everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008; 372: 449-56
64. Motzer RJ, Escudier B, Oudard S, et al. Phase 3 Trial of Everolimus for Metastatic Renal Cell Carcinoma. Cancer 2010; 116: 4256-65
65. Finke J, Ko J, Rini B, et al. MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy. Int Immuno-pharmacol 2011; 11: 853-8
66. Zhang L, Bhasin M, Schor-Bardach R, et al. Resistance of renal cell carcinoma to sorafenib is mediated by potentially reversible gene expression. PLoS One 2011; 6(4): e19144
67. Bhatt RS, Wang X, Zhang L, et al. Renal cancer resistance to antiangiogenic therapy is delayed by restoration of angiostatic signaling. Mol Cancer Ther 2010; 10: 2793-802
68. Porta C, Procopio G, Cartenì G, et al. Sequential use of sorafenib and sunitinib in advanced renal-cell carcinoma (RCC): an Italian multicentre retrospective analysis of 189 patient cases. BJU Int 2011
69. Garcia JA, Hutson TE, Elson P, et al. Sorafenib in patients with metastatic renal cell carcinoma refractory to either sunitinib or bevacizumab. Cancer 2010; 116: 5383-90
70. Rini BI, Wilding G, Hudes G, et al. Phase II study of axitinib in sorafenib-refractory metastatic renal cell carcinoma. J Clin Oncol 2009; 27: 4462-8
71. Zama IN, Hutson TE, Elson P, et al. Sunitinib rechallenge in metastatic renal cell carcinoma patients. Cancer 2010; 116: 5400-6
72. Rasmussen N, Rathmell WK. Looking beyond inhibition of VEGF/mTOR: Emerging targets for renal cell carcinoma drug development. Curr Clin Pharmacol 2011
73. Patel PH, Senico PL, Curiel RF, Motzer RJ. Phase I study combining treatment with Temsirolimus and Sunitinib in patients with Advanced Renal cell Carcinoma. Clinical Genitourinary Cancer 2009; 7: 24-27
74. Molina AM, Feldman DR, Ginsberg MS, et al. Phase I trial of sunitinib plus everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol 2011; 29(suppl 7; abstr 311)
75. Merchan JR, Pitot HC, Quin R, et al. Phase I/II trial of CCI 779 and bevacizumab in advanced renal cell carcinoma (RCC): Safety and activity in RTKI refractory RCC patients. J Clin Oncol 2009; 27: 15s, (suppl; abstr 5039)
76. Escudier B, Negrier S, Gravis S, et al. Can the combination of temsi-rolimus and bevacizumab improve the treatment of metastatic renal cell carcinoma (mRCC)? Results of the randomized TORAVA phase II trial. J Clin Oncol 2010; 28(15s): (suppl; abstr 4516)
77. Hainsworth JD, Spigel DR, Burris HA, et al. Phase II trial of bevacizumab and everolimus in patients with advanced renal cell carcinoma. J Cli Oncol 2010; 28: 2131-6
78. Sarbassovdos D, Ali SM, Sengupta S, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006; 22: 159-68
79. Wang X, Yue P, Kim YA, et al. Enhancing Mammalian Target of Rapamycin (mTOR)-Targeted Cancer Therapy by Preventing mTOR/Raptor Inhibition-Initiated, mTOR/Rictor-Independent Akt Activation. Cancer Res 2008; 68: 7409-18
80. Cho DC, Cohen MB, Panka DJ, et al. The efficacy of the novel dual PI3-Kinase/mTOR Inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma. Clin Cancer Res 2010; 16: 3628-38
81. Burris H, Rodon J, Sharma S, et al. First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors. J Clin Oncol 2010; 28(Suppl 15s): (abstr 3005)