Mammalian target of rapamycin

Seminars in Oncology

Volumn 31, Issue SUPPL. 16, 2004, Pages 10-17

  Meric Bernstam, Funda ^a   Mills, Gordon B ^a,b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; AP 23573; AP 23675; AP 23841; BCR ABL PROTEIN; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EVEROLIMUS; HYBRID PROTEIN; IMATINIB; PHOSPHATIDYLINOSITOL 3 KINASE; RAPAMYCIN; RETINOIC ACID; TEMSIROLIMUS; TRASTUZUMAB; UNCLASSIFIED DRUG;

BREAST CANCER; CANCER CELL; CANCER CHEMOTHERAPY; CANCER PATIENT; CANCER RADIOTHERAPY; CELL CYCLE; CLINICAL TRIAL; DIAGNOSTIC PROCEDURE; DISEASE COURSE; DISEASE MARKER; DRUG APPROVAL; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; DRUG SCREENING; DRUG SYNTHESIS; DRUG TARGETING; ENZYME ANALYSIS; GASTROINTESTINAL TOXICITY; GENE AMPLIFICATION; GENETIC ANALYSIS; GENETIC DISORDER; HUMAN; IMAGE ANALYSIS; INHIBITION KINETICS; MALIGNANT NEOPLASTIC DISEASE; MAMMAL; MOLECULAR BIOLOGY; MOLECULAR IMAGING; NONHUMAN; OUTCOMES RESEARCH; OVARY CANCER; PATHOPHYSIOLOGY; POPULATION GENETICS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; SKIN TOXICITY; TREATMENT OUTCOME; TUMOR;

EID: 12844271543     PISSN: 00937754     EISSN: None     Source Type: Journal    
DOI: 10.1053/j.seminoncol.2004.10.013     Document Type: Article

References (103)

1. G.B. Mills, E. Kohn, Y. Lu Linking molecular diagnostics to molecular therapeutics Targeting the PI3K pathway in breast cancer Semin Oncol 30 suppl 16 2003 93 104
2. D. Roymans, H. Slegers Phosphatidylinositol 3-kinases in tumor progression Eur J Biochem 268 2001 487 498
3. C.L. Carpenter, B.C. Duckworth, K.R. Auger Purification and characterization of phosphoinositide 3-kinase from rat liver J Biol Chem 265 1990 19704 19711
4. S. Paradis, M. Ailion, A. Toker A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans Genes Dev 13 1999 1438 1452
5. K.S. Cho, J.H. Lee, S. Kim Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway Proc Natl Acad Sci U S A 98 2001 6144 6149
6. T.O. Chan, P.N. Tsichlis PDK2 A complex tail in one Akt Sci STKE 2001 2001 PE1
7. M.J. Fry Phosphoinositide 3-kinase signalling in breast cancer How big a role might it play? Breast Cancer Res 3 2001 304 312
8. R. Parsons, L. Simpson PTEN and cancer Methods Mol Biol 222 2003 147 166
9. A.J. Philp, I.G. Campbell, C. Leet The phosphatidylinositol 3′-kinase p85alpha gene is an oncogene in human ovarian and colon tumors Cancer Res 61 2001 7426 7429
10. Y. Samuels, Z. Wang, A. Bardelli High frequency of mutations of the PIK3CA gene in human cancers Science 304 2004 554
11. A.B. Hui, K.W. Lo, X.L. Yin Detection of multiple gene amplifications in glioblastoma multiforme using array-based comparative genomic hybridization Lab Invest 81 2001 717 723
12. D.S. Byun, K. Cho, B.K. Ryu Frequent monoallelic deletion of PTEN and its reciprocal association with PIK3CA amplification in gastric carcinoma Int J Cancer 104 2003 318 327
13. L. Shayesteh, Y. Lu, W.L. Kuo PIK3CA is implicated as an oncogene in ovarian cancer Nat Genet 21 1999 99 102
14. Y.Y. Ma, S.J. Wei, Y.C. Lin PIK3CA as an oncogene in cervical cancer Oncogene 19 2000 2739 2744
15. A. Racz, N. Brass, D. Heckel Expression analysis of genes at 3q26-q27 involved in frequent amplification in squamous cell lung carcinoma Eur J Cancer 35 1999 641 646
16. J.Q. Cheng, A.K. Godwin, A. Bellacosa AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas Proc Natl Acad Sci U S A 89 1992 9267 9271
17. J.Q. Cheng, B. Ruggeri, W.M. Klein Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA Proc Natl Acad Sci U S A 93 1996 3636 3641
18. M. Sun, J.E. Paciga, R.I. Feldman Phosphatidylinositol-3-OH kinase (PI3K)/AKT2, activated in breast cancer, regulates and is induced by estrogen receptor alpha (ERalpha) via interaction between ERalpha and PI3K Cancer Res 61 2001 5985 5991
19. M. Barlund, F. Forozan, J. Kononen Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis J Natl Cancer Inst 92 2000 1252 1259
20. G. Choe, S. Horvath, T.F. Cloughesy Analysis of the phosphatidylinositol 3′-kinase signaling pathway in glioblastoma patients in vivo Cancer Res 63 2003 2742 2746
21. T.G. Ram, S.P. Ethier Phosphatidylinositol 3-kinase recruitment by p185erbB-2 and erb B-3 is potently induced by neu differentiation factor/heregulin during mitogenesis and is constitutively elevated in growth factor-independent breast carcinoma cells with c-erbB-2 gene amplification Cell Growth Differ 7 1996 551 561
22. M. Sattler, M.G. Mohi, Y.B. Pride Critical role for Gab2 in transformation by BCR/ABL Cancer Cell 1 2002 479 492
23. S. Lev, D. Givol, Y. Yarden A specific combination of substrates is involved in signal transduction by the kit-encoded receptor EMBO J 10 1991 647 654
24. R. Rottapel, M. Reedijk, D.E. Williams The Steel/W transduction pathway kit autophosphorylation and its association with a unique subset of cytoplasmic signaling proteins is induced by the Steel factor Mol Cell Biol 11 1991 3043 3051
25. R.A. Klinghoffer, B. Duckworth, M. Valius Platelet-derived growth factor-dependent activation of phosphatidylinositol 3-kinase is regulated by receptor binding of SH2-domain-containing proteins which influence Ras activity Mol Cell Biol 16 1996 5905 5914
26. S.P. Staal Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2 Amplification of AKT1 in a primary human gastric adenocarcinoma Proc Natl Acad Sci U S A 84 1987 5034 5037
27. H.K. Kwon, G.U. Bae, J.W. Yoon Constitutive activation of p70S6k in cancer cells Arch Pharm Res 25 2002 685 690
28. G.J. Wiederrecht, C.J. Sabers, G.J. Brunn Mechanism of action of rapamycin New insights into the regulation of G1-phase progression in eukaryotic cells Prog Cell Cycle Res 1 1995 53 71
29. M. Hidalgo, E.K. Rowinsky The rapamycin-sensitive signal transduction pathway as a target for cancer therapy Oncogene 19 2000 6680 6686
30. K. Hara, Y. Maruki, X. Long Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action Cell 110 2002 177 189
31. D.H. Kim, D. Sarbassov dos, S.M. Ali GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR Mol Cell 11 2003 895 904
32. A. Sekulic, C.C. Hudson, J.L. Homme A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells Cancer Res 60 2000 3504 3513
33. T.H. Reynolds, S.C. Bodine, J.C. Lawrence Jr Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load J Biol Chem 277 2002 17657 17662
34. K. Inoki, Y. Li, T. Zhu TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling Nat Cell Biol 4 2002 648 657
35. L.J. Saucedo, X. Gao, D.A. Chiarelli Rheb promotes cell growth as a component of the insulin/TOR signalling network Nat Cell Biol 5 2003 566 571
36. Y. Zhang, X. Gao, L.J. Saucedo Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins Nat Cell Biol 5 2003 578 581
37. H. Stocker, T. Radimerski, B. Schindelholz Rheb is an essential regulator of S6K in controlling cell growth in Drosophila Nat Cell Biol 5 2003 559 565
38. A. Garami, F.J. Zwartkruis, T. Nobukuni Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2 Mol Cell 11 2003 1457 1466
39. A.F. Castro, J.F. Rebhun, G.J. Clark Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase activation in a rapamycin- and farnesylation-dependent manner J Biol Chem 278 2003 32493 32496
40. G.J. Brunn, C.C. Hudson, A. Sekulic Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin Science 277 1997 99 101
41. K. Hara, K. Yonezawa, M.T. Kozlowski Regulation of eIF-4E BP1 phosphorylation by mTOR J Biol Chem 272 1997 26457 26463
42. A.C. Gingras, S.G. Kennedy, M.A. O'Leary 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway Genes Dev 12 1998 502 513
43. D.C. Fingar, C.J. Richardson, A.R. Tee mTOR controls cell cycle progression through its cell growth effectors S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E Mol Cell Biol 24 2004 200 216
44. J. Heitman, N.R. Movva, M.N. Hall Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast Science 253 1991 905 909
45. Y. Koltin, L. Faucette, D.J. Bergsma Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a peptidyl-prolyl cis-trans isomerase related to human FK506-binding protein Mol Cell Biol 11 1991 1718 1723
46. E.J. Brown, M.W. Albers, T.B. Shin A mammalian protein targeted by G1-arresting rapamycin-receptor complex Nature 369 1994 756 758
47. M.I. Chiu, H. Katz, V. Berlin RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex Proc Natl Acad Sci U S A 91 1994 12574 12578
48. D.M. Sabatini, H. Erdjument-Bromage, M. Lui RAFT1 A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs Cell 78 1994 35 43
49. D.A. Fruman, M.A. Wood, C.K. Gjertson FK506 binding protein 12 mediates sensitivity to both FK506 and rapamycin in murine mast cells Eur J Immunol 25 1995 563 571
50. C.J. Sabers, M.M. Martin, G.J. Brunn Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells J Biol Chem 270 1995 815 822
51. W.G. Morice, G. Wiederrecht, G.J. Brunn Rapamycin inhibition of interleukin-2-dependent p33cdk2 and p34cdc2 kinase activation in T lymphocytes J Biol Chem 268 1993 22737 22745
52. J. Nourse, E. Firpo, W.M. Flanagan Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin Nature 372 1994 570 573
53. Y. Luo, S.O. Marx, H. Kiyokawa Rapamycin resistance tied to defective regulation of p27Kip1 Mol Cell Biol 16 1996 6744 6751
54. S. Hashemolhosseini, Y. Nagamine, S.J. Morley Rapamycin inhibition of the G1 to S transition is mediated by effects on cyclin D1 mRNA and protein stability J Biol Chem 273 1998 14424 14429
55. S. Kawamata, H. Sakaida, T. Hori The upregulation of p27Kip1 by rapamycin results in G1 arrest in exponentially growing T-cell lines Blood 91 1998 561 569
56. A.L. Edinger, C.M. Linardic, G.G. Chiang Differential effects of rapamycin on mammalian target of rapamycin signaling functions in mammalian cells Cancer Res 63 2003 8451 8460
57. M. Guba, P. von Breitenbuch, M. Steinbauer Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis Involvement of vascular endothelial growth factor Nat Med 8 2002 128 135
58. S. Huang, P.J. Houghton Targeting mTOR signaling for cancer therapy Curr Opin Pharmacol 3 2003 371 377
59. H. Sun, R. Lesche, D.M. Li PTEN modulates cell cycle progression and cell survival by regulating phosphatidylinositol 3,4,5,-trisphosphate and Akt/protein kinase B signaling pathway Proc Natl Acad Sci U S A 96 1999 6199 6204
60. M.S. Neshat, I.K. Mellinghoff, C. Tran Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR Proc Natl Acad Sci U S A 98 2001 10314 10319
61. K. Podsypanina, R.T. Lee, C. Politis An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice Proc Natl Acad Sci U S A 98 2001 10320 10325
62. J. Li, C. Yen, D. Liaw PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer Science 275 1997 1943 1947
63. M. Hidalgo, E. Rowinsky, C. Erlichman CCI-779, a rapamycin analog and multifaceted inhibitor of signal transduction A phase I study Proc Am Soc Clin Oncol 19 2000 187a (abstr 726)
64. M.B. Atkins, M. Hidalgo, W. Stadler A randomized double-blind phase 2 study of intravenous CCI-779 administered weekly to patients with advanced renal cell carcinoma Proc Am Soc Clin Oncol 21 2002 10a (abstr 36)
65. J.P. Dutcher, G. Hudes, R. Motzer Preliminary report of a phase 1 study of intravenous (IV) CCI-779 given in combination with interferon-a (IFN) to patients with advanced renal cell carcinoma (RCC) Proc Am Soc Clin Oncol 22 2003 213 (abstr 854)
66. S. Chan, M.E. Scheulen, S. Johnston Final results of a phase 2 study of single-agent CCI-779 in locally advanced or metastatic breast cancer failing prior anthracycline and/or taxane regimens Breast Cancer Res Treat 82 2003 S82
67. M.B. Atkins, M. Hidalgo, W.M. Stadler 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 22 2004 909 918
68. T.E. Witzig, S.M. Geyer, S. Muhammed A phase II trial of the rapamycin analog CCI-779 in previously treated mantle cell non-Hodgkin's lymphoma Interim analysis of 18 patients Proc Am Soc Hematol 102 2003 643a (abstr 2374)
69. E. Buchdunger, J. Zimmermann, H. Mett Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative Cancer Res 56 1996 100 104
70. H. Kantarjian, C. Sawyers, A. Hochhaus Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia N Engl J Med 346 2002 645 652
71. S.G. O'Brien, F. Guilhot, R.A. Larson Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia N Engl J Med 348 2003 994 1004
72. C.L. Sawyers, A. Hochhaus, E. Feldman Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis Results of a phase II study Blood 99 2002 3530 3539
73. M.C. Heinrich, D.J. Griffith, B.J. Druker Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor Blood 96 2000 925 932
74. K. Kikuchi, Y. Soma, M. Fujimoto Dermatofibrosarcoma protuberans Increased growth response to platelet-derived growth factor BB in cell culture Biochem Biophys Res Commun 196 1993 409 415
75. J. Cools, D.J. DeAngelo, J. Gotlib A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome N Engl J Med 348 2003 1201 1214
76. M.C. Heinrich, C.L. Corless, G.D. Demetri Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor J Clin Oncol 21 2003 4342 4349
77. G.B. Mills, Y. Lu, E.C. Kohn Linking molecular therapeutics to molecular diagnostics Inhibition of the FRAP/RAFT/TOR component of the PI3K pathway preferentially blocks PTEN mutant cells in vitro and in vivo Proc Natl Acad Sci U S A 98 2001 10031 10033
78. Y. Shi, J. Gera, L. Hu Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI-779 Cancer Res 62 2002 5027 5034
79. I.M. Ghobrial, D.A. Loegering, M.J. Stenson CCI-779 inhibits phosphorylation of ribosomal S6 (pS6) in mantle cell lymphoma Proc Am Assoc Cancer Res 45 2004 850 (abstr 3686)
80. W.C. Noh, W.H. Mondesire, J. Peng Determinants of rapamycin sensitivity in breast cancer cells Clin Cancer Res 10 2004 1013 1023
81. K. Yu, L. Toral-Barza, C. Discafani mTOR, a novel target in breast cancer The effect of CCI-779, an mTOR inhibitor, in preclinical models of breast cancer Endocr Relat Cancer 8 2001 249 258
82. S. Di Cosimo, P. Matar, F. Rojo The mTOR pathway inhibitor RAD001 induces activation of AKT which is completely abolished by Gefitinib, an anti-EGFR tyrosine kinase inhibitor, and combined sequence specific treatment results in greater antitumor activity Proc Am Assoc Cancer Res 45 2004 1233 (abstr 5345)
83. F. Meric, M.C. Hung, G.N. Hortobagyi HER2/neu in the management of invasive breast cancer J Am Coll Surg 194 2002 488 501
84. G. Xu, W. Zhang, P. Bertram Pharmacogenomic profiling of the PI3K/PTEN-AKT-mTOR pathway in common human tumors Int J Oncol 24 2004 893 900
85. J.M. Peralba, L. DeGraffenried, W. Friedrichs Pharmacodynamic evaluation of CCI-779, an inhibitor of mTOR, in cancer patients Clin Cancer Res 9 2003 2887 2892
86. A. Boulay, S. Zumstein-Mecker, C. Stephan 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 64 2004 252 261
87. J. Shao, B.M. Evers, H. Sheng Roles of phosphatidylinositol 3′-kinase and mammalian target of rapamycin/p70 ribosomal protein S6 kinase in K-Ras-mediated transformation of intestinal epithelial cells Cancer Res 64 2004 229 235
88. J.F. Gera, I.K. Mellinghoff, Y. Shi AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression J Biol Chem 279 2004 2737 2746
89. H.L. Kenerson, L.D. Aicher, L.D. True Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors Cancer Res 62 2002 5645 5650
90. R.K. Hall, D.K. Granner Insulin regulates expression of metabolic genes through divergent signaling pathways J Basic Clin Physiol Pharmacol 10 1999 119 133
91. A. Guenther, F. Bakker, A. Wohlfarth mTOR inhibitor rapamycin is active for treatment of plasma cell tumors Proc Am Soc Clin Oncol 22 2003 218 (abstr 956)
92. M.G. Mohi, C. Boulton, T.L. Gu Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs Proc Natl Acad Sci U S A 101 2004 3130 3135
93. C.J. Bruns, G.E. Koehl, M. Guba Rapamycin-induced endothelial cell death and tumor vessel thrombosis potentiate cytotoxic therapy against pancreatic cancer Clin Cancer Res 10 2004 2109 2119
94. T. Stromberg, A. Dimberg, A. Hammarberg Rapamycin sensitizes multiple myeloma cells to apoptosis induced by dexamethasone Blood 103 2004 3138 3147
95. L. Wu, D.C. Birle, I.F. Tannock Effects of the mTOR inhibitor CCI-779 used alone or during chemotherapy on human prostate cancer xenografts Proc Am Assoc Cancer Res 45 2004 888 (abstr 3849)
96. V.M. Rivera, H. Tang, A. Chester Anti-proliferative activity of the mTOR inhibitor AP23573 in combination with cytotoxic and targeted agents Proc Am Assoc Cancer Res 45 2004 896 (abstr)
97. V.A. Papadimitrakopoulou, S. Lnu, E. Brown Combined effects if inhibition of mTOR and EGFR signaling on apoptosis and kinase pathways in nonsmall cell lung cancer cell lines Proc Am Assoc Cancer Res 45 2004 1116 (abstr 4833)
98. D. Ito, K. Fujimoto, R. Doi mTOR, a novel target in pancreatic cancer The effect of CCI-779 in preclinical models Proc Am Assoc Cancer Res 45 2004 896 (abstr 3886)
99. J. Rudloff, A. Boulay, S. Zumstein-Mecker The mTOR pathway in estrogen response A potential for combining the rapamycin derivative RAD001 with the aromatase inhibitor letrozole (Femara) in breast carcinoma Proc Am Assoc Cancer Res 45 2004 1298 (abstr 5619)
100. B. Geoerger, K. Kerr, C.B. Tang Antitumor activity of the rapamycin analog CCI-779 in human primitive neuroectodermal tumor/medulloblastoma models as single agent and in combination chemotherapy Cancer Res 61 2001 1527 1532
101. Y. Shi, A. Frankel, L.G. Radvanyi Rapamycin enhances apoptosis and increases sensitivity to cisplatin in vitro Cancer Res 55 1995 1982 1988
102. V. Grunwald, L. DeGraffenried, D. Russel Inhibitors of mTOR reverse doxorubicin resistance conferred by PTEN status in prostate cancer cells Cancer Res 62 2002 6141 6145
103. H.G. Wendel, E. De Stanchina, J.S. Fridman Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy Nature 428 2004 332 337