Current Problems in Cancer
Volume 32, Issue 4 , Pages 161-177 , July 2008

Mammalian Target of Rapamycin as a Target in Hematological Malignancies

References 

  1. Meijer AJ, Dubbelhuis PF. Amino acid signalling and the integration of metabolism. Biochem Biophys Res Commun. 2004;313(2):397–403
  2. Long X, Muller F, Avruch J. TOR action in mammalian cells and in Caenorhabditis elegans. Curr Top Microbiol Immunol. 2004;279:115–138
  3. Gingras AC, Raught B, Sonenberg N. mTOR signaling to translation. Curr Top Microbiol Immunol. 2004;279:169–197
  4. Fingar DC, Richardson CJ, Tee AR, et al. mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E. Mol Cell Biol. 2004;24(1):200–216
  5. Schmelzle T, Hall MN. TOR, a central controller of cell growth. [see comment] Cell. 2000;103(2):253–262
  6. Gingras AC, Raught B, Sonenberg N. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 2001;15(7):807–826
  7. 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(2):815–822
  8. Sabatini DM, Erdjument-Bromage H, Lui M, et al. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell. 1994;78(1):35–43
  9. Chiu MI, Katz H, Berlin V. RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. Proc Natl Acad Sci U S A. 1994;91(26):12574–12578
  10. Brown EJ, Albers MW, Shin TB, et al. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature. 1994;369(6483):756–758
  11. Jacinto E, Hall MN. Tor signalling in bugs, brain and brawn. Nat Rev Mol Cell Biol. 2003;4(2):117–126[Published erratum appears in Nat Rev Mol Cell Biol 2003;4(3):249.]
  12. Abraham RT. Identification of TOR signaling complexes: more TORC for the cell growth engine. Cell. 2002;111(1):9–12
  13. Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem. 1998;31(5):335–340[Reprint in Clin Biochem 2006;39(5):484-9, PMID: 16783879.]
  14. Vezina C, Kudelski A, Sehgal SN. Rapamycin (AY-22989), a new antifungal antibiotic (I. Taxonomy of the producing streptomycete and isolation of the active principle). J Antibiot. 1975;28(10):721–726
  15. Sehgal SN, Baker H, Vezina C. Rapamycin (AY-22989), a new antifungal antibiotic (II. Fermentation, isolation and characterization). J Antibiot. 1975;28(10):727–732
  16. Calne RY, Collier DS, Lim S, et al. Rapamycin for immunosuppression in organ allografting. [see comment] Lancet. 1989;2(8656):227
  17. Augustine JJ, Bodziak KA, Hricik DE. Use of sirolimus in solid organ transplantation. Drugs. 2007;67(3):369–391
  18. Temsirolimus: CCI 779, CCI-779, cell cycle inhibitor-779. Drugs R D. 2004;5(6):363–367
  19. Steffel J, Latini RA, Akhmedor A, et al. Rapamycin, but not FK-506, increases endothelial tissue factor expression: implications for drug-eluting stent design. Circulation. 2005;112(13):2002–2011
  20. Eng CP, Sehgal SN, Vezina C. Activity of rapamycin (AY-22989) against transplanted tumors. J Antibiot. 1984;37(10):1231–1237
  21. Houchens DP, Ovejera AA, Riblet SM, et al. Human brain tumor xenografts in nude mice as a chemotherapy model. Eur J Cancer Clin Oncol. 1983;19(6):799–805
  22. Douros J, Suffness M. New antitumor substances of natural origin. Cancer Treat Rev. 1981;8(1):63–87
  23. Huang S, Houghton PJ. Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol. 2003;3(4):371–377
  24. Dennis PB, Thomas G. Quick guide: target of rapamycin. Curr Biol. 2002;12(8):R269
  25. Sarkaria JN, Busby EC, Tibbetts RS, et al. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res. 1998;58(19):4375–4382
  26. Yuille MA, Coignet LJ. The ataxia telangiectasia gene in familial and sporadic cancer. Recent Results Cancer Res. 1998;154:156–173
  27. Kim DH, Sarbassor DD, Ali SM, et al. GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell. 2003;11(4):895–904
  28. Hara K, Maruki Y, Long X, et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002;110(2):177–189
  29. Kim DH, Sarbassor 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(2):163–175
  30. Yonezawa K, Tokunaga C, Oshiro N, et al. Raptor, a binding partner of target of rapamycin. Biochem Biophys Res Commun. 2004;313(2):437–441
  31. Harris TE, Lawrence JC. TOR signaling. Science's Stke [Electronic Resource]: Signal Transduction Knowledge Environment, 2003. 2003;212:re15
  32. Nojima H, Tokunaga C, Eguchi S, et al. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem. 2003;278(18):15461–15464
  33. Proud CG. mTOR-mediated regulation of translation factors by amino acids. Biochem Biophys Res Commun. 2004;313(2):429–436
  34. Yonezawa K, Yoshino KI, Tokunaga C, et al. Kinase activities associated with mTOR. Curr Top Microbiol Immunol. 2004;279:271–282
  35. Sarbassov DD, Ali SM, Kim DH, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004;14(14):1296–1302
  36. Sarbassov DD, Guertin DA, Ali SM, et al. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307(5712):1098–1101
  37. 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(25):3958–3964
  38. Mabuchi S, Altomare DA, Connolly DC, et al. RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Res. 2007;67(6):2408–2413
  39. Karbowniczek M, Spittle CS, Morrison T, Wu H, Henske EP. mTOR is activated in the majority of malignant melanomas. J Invest Dermatol. 2008;128(4):980–987
  40. Johnson BE, Jackman D, Janne PA. Rationale for a phase I trial of erlotinib and the mammalian target of rapamycin inhibitor everolimus (RAD001) for patients with relapsed non small cell lung cancer. Clin Cancer Res. 2007;13(15):s4628–s4631
  41. Fouladi M, Laningham F, Wu J, et al. Phase I study of everolimus in pediatric patients with refractory solid tumors. J Clin Oncol. 2007;25(30):4806–4812
  42. Costa LJ. Aspects of mTOR biology and the use of mTOR inhibitors in non-Hodgkin's lymphoma. Cancer Treat Rev. 2007;33(1):78–84
  43. 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(2):758s–763s
  44. Yee KW, Zeng Z, Konoplera M, et al. Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies. Clin Cancer Res. 2006;12(17):5165–5173
  45. Hynes NE, Boulay A. The mTOR pathway in breast cancer. J Mammary Gland Biol Neoplasia. 2006;11(1):53–61
  46. Panwalkar A, Verstovsek S, Giles FJ. Mammalian target of rapamycin inhibition as therapy for hematologic malignancies. Cancer. 2004;100(4):657–666
  47. Dancey JE. mTOR inhibitors in hematologic malignancies. Clin Adv Hematol Oncol. 2003;1(7):419–423
  48. Herberger B, Puhalla H, Lehnert M, et al. Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma. Clin Cancer Res. 2007;13(16):4795–4799
  49. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007;12(1):9–22
  50. Hutson TE, Figlin RA. Evolving role of novel targeted agents in renal cell carcinoma. Oncology. 2007;21(10):1175–1180
  51. Brown RE, Zhang PL, Lun M, et al. Morphoproteomic and pharmacoproteomic rationale for mTOR effectors as therapeutic targets in head and neck squamous cell carcinoma. Ann Clin Lab Sci. 2006;36(3):273–282
  52. Clark PE. Recent advances in targeted therapy for renal cell carcinoma. Curr Opin Urol. 2007;17(5):331–336
  53. Kobayashi S, Kishimoto T, Kamata S, et al. Rapamycin, a specific inhibitor of the mammalian target of rapamycin, suppresses lymphangiogenesis and lymphatic metastasis. Cancer Sci. 2007;98(5):726–733
  54. Huber S, Bruns CJ, Schmid G, et al. Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis. Kidney Int. 2007;71(8):771–777
  55. Nathan CO, Amirghahari N, Rong X, et al. Mammalian target of rapamycin inhibitors as possible adjuvant therapy for microscopic residual disease in head and neck squamous cell cancer. Cancer Res. 2007;67(5):2160–2168
  56. Buck E, Eyzaguirre A, Brown E, et al. Rapamycin synergizes with the epidermal growth factor receptor inhibitor erlotinib in non-small-cell lung, pancreatic, colon, and breast tumors. Mol Cancer Ther. 2006;5(11):2676–2684
  57. Chollet P, Abrial C, Tacca O, et al. Mammalian target of rapamycin inhibitors in combination with letrozole in breast cancer. Clin Breast Cancer. 2006;7(4):336–338
  58. Martelli AM, Tazzari PL, Evangelisti C, et al. Targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin module for acute myelogenous leukemia therapy: from bench to bedside. Curr Med Chem. 2007;14(19):2009–2023
  59. Follo MY, Mongiorgi S, Bosi C, et al. The Akt/mammalian target of rapamycin signal transduction pathway is activated in high-risk myelodysplastic syndromes and influences cell survival and proliferation. Cancer Res. 2007;67(9):4287–4294
  60. Xu Q, Thompson JE, Carroll M. mTOR regulates cell survival after etoposide treatment in primary AML cells. Blood. 2005;106(13):4261–4268
  61. Wanner K, Hipp S, Oelsner M, et al. Mammalian target of rapamycin inhibition induces cell cycle arrest in diffuse large B cell lymphoma (DLBCL) cells and sensitises DLBCL cells to rituximab. Br J Haematol. 2006;134(5):475–484
  62. Vega F, Medeiros LJ, Leventaki V, et al. Activation of mammalian target of rapamycin signaling pathway contributes to tumor cell survival in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. Cancer Res. 2006;66(13):6589–6597
  63. Kawamata N, Chen J, Koeffler HP. Suberoylanilide hydroxamic acid (SAHA; vorinostat) suppresses translation of cyclin D1 in mantle cell lymphoma cells. Blood. 2007;110(7):2667–2673
  64. Huyghe E, Zairi A, Nohra J, et al. Gonadal impact of target of rapamycin inhibitors (sirolimus and everolimus) in male patients: an overview. Transpl Int. 2007;20(4):305–311
  65. Deutsch MA, Kaczmarek I, Huber S, et al. Sirolimus-associated infertility: case report and literature review of possible mechanisms. Am J Transplant. 2007;7(10):2414–2421
  66. Pallet N, Thervet E, Legendre C, et al. [Nephrotoxicity of sirolimus: experimental and clinical data]. Nephrol Ther. 2006;2(4):183–190
  67. Rangan GK. Sirolimus-associated proteinuria and renal dysfunction. Drug Saf. 2006;29(12):1153–1161
  68. Boni J, Leister C, Burns J, et al. Pharmacokinetic profile of temsirolimus with concomitant administration of cytochrome P450-inducing medications. J Clin Pharmacol. 2007;47(11):1430–1439
  69. Duran I, Siu LL, Oza AM, et al. Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus. Eur J Cancer. 2006;42(12):1875–1880
  70. Tenderich G, Fuchs U, Zittermann A, et al. Comparison of sirolimus and everolimus in their effects on blood lipid profiles and haematological parameters in heart transplant recipients. Clin Transplant. 2007;21(4):536–543
  71. Fruman DA, Wood MA, Gjertson CK, et al. FK506 binding protein 12 mediates sensitivity to both FK506 and rapamycin in murine mast cells. Eur J Immunol. 1995;25(2):563–571
  72. Luo Y, Marx SO, Kiyokawa H, et al. Rapamycin resistance tied to defective regulation of p27Kip1. Mol Cell Biol. 1996;16(12):6744–6751
  73. Shima H, Pende M, Chen Y, et al. Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J. 1998;17(22):6649–6659
  74. Dilling MB, Germain GS, Dudkin L, et al. 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. J Biol Chem. 2002;277(16):13907–13917
  75. Dennis PB, Pullen N, Kozma SC, et al. The principal rapamycin-sensitive p70(s6k) phosphorylation sites, T-229 and T-389, are differentially regulated by rapamycin-insensitive kinase kinases. Mol Cell Biol. 1996;16(11):6242–6251
  76. Sugiyama H, Papst P, Gelfand EW, et al. p70 S6 kinase sensitivity to rapamycin is eliminated by amino acid substitution of Thr229. J Immunol. 1996;157(2):656–660
  77. Huang S, Shu L, Dilling MB, et al. Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1). Mol Cell. 2003;11(6):1491–1501
  78. Kurmasheva RT, Huang S, Houghton PJ. Predicted mechanisms of resistance to mTOR inhibitors. Br J Cancer. 2006;95(8):955–960
  79. Beamish H, Williams R, Chen P, et al. Rapamycin resistance in ataxia-telangiectasia. Oncogene. 1996;13(5):963–970
  80. Bertram PG, Zeng C, Thorson J, et al. The 14-3-3 proteins positively regulate rapamycin-sensitive signaling. Curr Biol. 1998;8(23):1259–1267
  81. O'Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006;66(3):1500–1508
  82. Dumont FJ, Staruch MJ, Grammer T, et al. Dominant mutations confer resistance to the immunosuppressant, rapamycin, in variants of a T cell lymphoma. Cell Immunol. 1995;163(1):70–79
  83. Hammerman PS, Fox CJ, Birnbaum MJ, et al. Pim and Akt oncogenes are independent regulators of hematopoietic cell growth and survival. Blood. 2005;105(11):4477–4483
  84. Shi Y, Gera J, Hu L, et al. Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI-779. Cancer Res. 2002;62(17):5027–5034
  85. Peponi E, Drakos E, Reyes G, et al. Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma. Am J Pathol. 2006;169(6):2171–2180
  86. Goy A, Feldman T. Expanding therapeutic options in mantle cell lymphoma. Clin Lymphoma Myeloma. 2007;7(suppl 5):S184–S191
  87. Hipp S, Ringshausen I, Oelsner M, et al. Inhibition of the mammalian target of rapamycin and the induction of cell cycle arrest in mantle cell lymphoma cells. Haematologica. 2005;90(10):1433–1434
  88. Baumann P, Mandl-Weber S, Emmerich B, et al. Activation of adenosine monophosphate activated protein kinase inhibits growth of multiple myeloma cells. Exp Cell Res. 2007;313(16):3592–3603
  89. Strömberg T, Dimberg A, Hammarberg A, et al. Rapamycin sensitizes multiple myeloma cells to apoptosis induced by dexamethasone. Blood. 2004;103(8):3138–3147
  90. Yan H, Frost P, Shi Y, et al. Mechanism by which mammalian target of rapamycin inhibitors sensitize multiple myeloma cells to dexamethasone-induced apoptosis. Cancer Res. 2006;66(4):2305–2313
  91. Francis LK, Alsayed Y, Leleu X, et al. Combination mammalian target of rapamycin inhibitor rapamycin and HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin has synergistic activity in multiple myeloma. Clin Cancer Res. 2006;12(22):6826–6835
  92. Avellino R, Romano S, Parasole R, et al. Rapamycin stimulates apoptosis of childhood acute lymphoblastic leukemia cells. Blood. 2005;106(4):1400–1406
  93. Thomas X. Emerging drugs for adult acute lymphoblastic leukaemia. Expert Opin Emerg Drugs. 2005;10(3):591–617
  94. Brown VI, Fang J, Alcom K, et al. Rapamycin is active against B-precursor leukemia in vitro and in vivo, an effect that is modulated by IL-7-mediated signaling. Proc Natl Acad Sci U S A. 2003;100(25):15113–15118
  95. Lal L, Li Y, Smith J, et al. Activation of the p70 S6 kinase by all-trans-retinoic acid in acute promyelocytic leukemia cells. Blood. 2005;105(4):1669–1677
  96. Dos Santos C, Récher C, Demur C, et al. [The PI3K/Akt/mTOR pathway: a new therapeutic target in the treatment of acute myeloid leukemia]. Bull Cancer. 2006;93(5):445–447
  97. Récher C, Beyne-Rauzy O, Demur C, et al. Antileukemic activity of rapamycin in acute myeloid leukemia. Blood. 2005;105(6):2527–2534
  98. Récher C, Dos Santos C, Demur C, et al. mTOR, a new therapeutic target in acute myeloid leukemia. Cell Cycle. 2005;4(11):1540–1549
  99. Xu RH, Pelicano H, Zhang H, et al. Synergistic effect of targeting mTOR by rapamycin and depleting ATP by inhibition of glycolysis in lymphoma and leukemia cells. Leukemia. 2005;19(12):2153–2158
  100. Yoon P, Giafis N, Smith J, et al. Activation of mammalian target of rapamycin and the p70 S6 kinase by arsenic trioxide in BCR-ABL-expressing cells. Mol Cancer Ther. 2006;5(11):2815–2823
  101. Ly C, Arechiga AF, Melo JV, et al. Bcr-Abl kinase modulates the translation regulators ribosomal protein S6 and 4E-BP1 in chronic myelogenous leukemia cells via the mammalian target of rapamycin. Cancer Res. 2003;63(18):5716–5722
  102. Burchert A, Wang Y, Cai D, et al. Compensatory PI3-kinase/Akt/mTor activation regulates imatinib resistance development. Leukemia. 2005;19(10):1774–1782
  103. Mayerhofer M, Aichberger KJ, Florian S, et al. Identification of mTOR as a novel bifunctional target in chronic myeloid leukemia: dissection of growth-inhibitory and VEGF-suppressive effects of rapamycin in leukemic cells. FASEB J. 2005;19(8):960–962
  104. Parmar S, Smith J, Sassano A, et al. Differential regulation of the p70 S6 kinase pathway by interferon alpha (IFNalpha) and imatinib mesylate (STI571) in chronic myelogenous leukemia cells. Blood. 2005;106(7):2436–2443
  105. Jundt F, Raetzel N, Müller C, et al. A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas. Blood. 2005;106(5):1801–1807
  106. Ringshausen I, Peschel C, Decker T. Mammalian target of rapamycin (mTOR) inhibition in chronic lymphocytic B-cell leukemia: a new therapeutic option. Leuk Lymphoma. 2005;46(1):11–19
  107. Leseux L, Hamdi SM, Al Saati T, et al. Syk-dependent mTOR activation in follicular lymphoma cells. Blood. 2006;108(13):4156–4162
  108. 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(12):2336–2347
  109. 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(19):5755–5763
  110. 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(5):909–918
  111. Peralba JM, DeGraffenreid L, Friedrichs W, et al. Pharmacodynamic evaluation of CCI-779, an inhibitor of mTOR, in cancer patients. Clin Cancer Res. 2003;9(8):2887–2892
  112. 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(23):5347–5356
  113. Grube E, Gerckens U, Buellesfeld L. Drug-eluting stents: clinical experiences and perspectives. Minerva Cardioangiol. 2002;50(5):469–473
  114. Majewski M, Korecka M, Kossev P, et al. The immunosuppressive macrolide RAD inhibits growth of human Epstein-Barr virus-transformed B lymphocytes in vitro and in vivo: a potential approach to prevention and treatment of posttransplant lymphoproliferative disorders. Proc Natl Acad Sci U S A. 2000;97(8):4285–4290
  115. Eisen HJ, Tuzcu EM, Dorent R, et al. Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients. N Engl J Med. 2003;349(9):847–858
  116. Majewski M, Korecka M, Joergensen J, et al. Immunosuppressive TOR kinase inhibitor everolimus (RAD) suppresses growth of cells derived from posttransplant lymphoproliferative disorder at allograft-protecting doses. Transplantation. 2003;75(10):1710–1717
  117. Azzola A, Havry KA, Chhajed P, et al. Everolimus and mycophenolate mofetil are potent inhibitors of fibroblast proliferation after lung transplantation. Transplantation. 2004;77(2):275–280
  118. Pascual J. Everolimus in clinical practice: renal transplantation. Nephrol Dial Transplant. 2006;21(suppl 3):iii18–iii23
  119. Kirchner GI, Meier-Wiedenbach I, Manns MP. Clinical pharmacokinetics of everolimus. Clin Pharmacokinet. 2004;43(2):83–95
  120. Boulay A, Zumstein-Mecker S, Stephan C, et al. Antitumor efficacy of intermittent treatment schedules with the rapamycin derivative RAD001 correlates with prolonged inactivation of ribosomal protein S6 kinase 1 in peripheral blood mononuclear cells. Cancer Res. 2004;64(1):252–261
  121. Haritunians T, Mori A, O'Kelly J, et al. Antiproliferative activity of RAD001 (everolimus) as a single agent and combined with other agents in mantle cell lymphoma. Leukemia. 2007;21(2):333–339
  122. Feldman E, Giles F, Roboz G, et al. A phase 2 clinical trial of AP23573, an mTOR inhibitor, in patients with relapsed or refractory hematologic malignancies. J Clin Oncol 2005 ASCO Annual Meeting Proceedings. Vol 23, No. 16S, Part I of II (June 1 Supplement), Abstract 6631, 2005.
  123. Rizzieri DA, Feldman E, Moore JO, et al. A phase 2 clinical trial of AP23573, an mTOR inhibitor, in patients with relapsed or refractory hematologic malignancies. Blood. 2005;106(11):Abstract 2980

PII: S0147-0272(08)00032-9

doi: 10.1016/j.currproblcancer.2008.05.001

Current Problems in Cancer
Volume 32, Issue 4 , Pages 161-177 , July 2008

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