mTOR and cancer therapy

Oncogene

Volumn 25, Issue 48, 2006, Pages 6436-6446

  Easton, J B ^a   Houghton, P J ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

Autophagy; Cancer therapy; Hypoxia; mTOR; Rapamycin; Stem cells

Indexed keywords

ALPHA INTERFERON; AMINOTRANSFERASE; AP 23573; AROMATASE INHIBITOR; BEVACIZUMAB; CYTARABINE; DOXORUBICIN; ERLOTINIB; EVEROLIMUS; GEFITINIB; IMATINIB; LENALIDOMIDE; LETROZOLE; MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; OCTREOTIDE; RAPAMYCIN; RAPAMYCIN DERIVATIVE; RITUXIMAB; TEMSIROLIMUS; THALIDOMIDE DERIVATIVE; TRASTUZUMAB;

AMINOTRANSFERASE BLOOD LEVEL; AUTOPHAGY; CANCER GROWTH; CANCER THERAPY; CELL PROLIFERATION; CLINICAL TRIAL; DRUG EFFECT; DRUG MECHANISM; DRUG TOLERABILITY; GROWTH REGULATION; HUMAN; HYPOCALCEMIA; HYPOXIA; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN TARGETING; REVIEW; STEM CELL; THROMBOCYTOPENIA; VOMITING;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; AUTOPHAGY; CELL HYPOXIA; ENZYME ACTIVATION; HUMANS; NEOPLASMS; PROTEIN KINASES; SIROLIMUS; STEM CELLS;

MAMMALIA;

EID: 33750072949     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/sj.onc.1209886     Document Type: Review

References (88)

1. Arsham AM, Howell JJ, Simon MC. (2003). A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets. J Biol Chem 278: 29655-29660.
2. Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR et al. (2004). 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: 909-918.
3. Bader AG, Felts KA, Jiang N, Chang HW, Vogt PK. (2003). Y box-binding protein 1 induces resistance to oncogenic transformation by the phosphatidylinositol 3-kinase pathway. Proc Natl Acad Sci USA 100: 12384-12389.
4. Barata JT, Cardoso AA, Nadler LM, Boussiotis VA. (2001). Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27(kip1). Blood 98: 1524-1531.
5. Berkel HJ, Turbat-Herrera EA, Shi R, de Benedetti A. (2001). Expression of the translation initiation factor eIF4E in the polyp-cancer sequence in the colon. Cancer Epidemiol Biomarkers Prev 10: 663-666.
6. Bjornsti M-A, Houghton PJ. (2004). The TOR pathway: a target for cancer therapy. Nat Rev Cancer 4: 335-348.
7. Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E et al. (2004). Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 18: 2893-2904.
8. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS et al. (1999). Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell 96: 857-868.
9. Bursch W, Ellinger A, Kienzl H, Torok L, Pandey S, Sikorska M et al. (1996). Active cell death induced by the antiestrogens tamoxifen and ICI 164 384 in human mammary carcinoma cells (MCF-7) in culture: the role of autophagy. Carcinogenesis 17: 1595-1607.
10. Chan S, Scheulen ME, Johnston S, Mross K, Cardoso F, Dittrich C et al. (2005). Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer. J Clin Oncol 23: 5314-5322.
11. Choi J, Chen J, Schreiber SL, Clardy J. (1996). Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science 273: 239-242.
12. Connolly E, Braunstein S, Formenti S, Schneider RJ. (2006). Hypoxia inhibits protein synthesis through a 4E-BP1 and elongation factor 2 kinase pathway controlled by mTOR and uncoupled in breast cancer cells. Mol Cell Biol 26: 3955-3965.
13. Costa LF, Balcells M, Edelman ER, Nadler LM, Cardoso AA. (2006). Proangiogenic stimulation of bone marrow endothelium engages mTOR and is inhibited by simultaneous blockade of mTOR and NF-{kappa}B. Blood 107: 285-292.
14. Couch FJ, Wang XY, Wu GJ, Qian J, Jenkins RB, James CD. (1999). Localization of PS6K to chromosomal region 17q23 and determination of its amplification in breast cancer. Cancer Res 59: 1408-1411.
15. Crew JP, Fuggle S, Bicknell R, Cranston DW, de Benedetti A, Harris AL. (2000). Eukaryotic initiation factor-4E in superficial and muscle invasive bladder cancer and its correlation with vascular endothelial growth factor expression and tumour progression. Br J Cancer 82: 161-166.
16. Cross DAE, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. (1995). Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378: 785-789.
17. Dancey JE. (2002). Clinical development of mammalian target of rapamycin inhibitors. Hematol Oncol Clin North Am 16: 1101-1114.
18. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y et al. (1997). Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91: 231-241.
19. deGraffenried LA, Friedrichs WE, Russell DH, Donzis EJ, Middleton AK, Silva JM et al. (2004). Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt activity. Clin Cancer Res 10: 8059-8067.
20. Dilling MB, Germain GS, Dudkin L, Jayaraman AL, Zhang X, Harwood FC et al. (2002). 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are downregulated in cells with acquired or intrinsic resistance to rapamycin. J Biol Chem 277: 13907-13917.
21. Edwards E, Geng L, Tan J, Onishko H, Donnelly E, Hallahan DE. (2002). Phosphatidylinositol 3-kinase/Akt signaling in the response of vascular endotheliumto ionizing radiation. Cancer Res 62: 4671-4677.
22. Gemmill RM, Zhou M, Costa L, Korch C, Bukowski RM, Drabkin HA. (2005). Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma. Br J Cancer 92: 2266-2277.
23. Giardiello FM, Welsh SB, Hamilton SR, Offerhaus GJ, Gittelsohn AM, Booker SV et al. (1987). Increased risk of cancer in the Peutz-Jeghers syndrome. N Engl J Med 316: 1511-1514.
24. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN et al. (2001). Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293: 876-880.
25. Guba M, von Breitenbuch P, Steinbauer M, Koehl G, Flegel S, Hornung M et al. (2002). Rapamycin inhibits primary and metastatic tumor growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat Med 8: 128-135.
26. Hamanaka Y, Mukai M, Shimamura M, Kitagawa T, Nishida T, Isohashi F et al. (2005). Suppression of PI3K/mTOR pathway rescues LLC cells fromcell death induced by hypoxia. Biochem Biophys Res Commun 330: 318-326.
27. Haydon MS, Googe JD, Sorrells DS, Ghali GE, Li BD. (2000). Progression of eIF4e gene amplification and overexpression in benign and malignant tumors of the head and neck. Cancer 88: 2803-2810.
28. Hentges KE, Sirry B, Gingeras AC, Sarbassov D, Sonenberg N, Sabatini D et al. (2001). FRAP/mTOR is required for proliferation and patterning during embryonic development in the mouse. Proc Natl Acad Sci USA 98: 13796-13801.
29. Huang S, Liu LN, Hosoi H, Dilling MB, Shikata T, Houghton PJ. (2001). p53/p21(CIP1) cooperate in enforcing rapamycin-induced G(1) arrest and determine the cellular response to rapamycin. Cancer Res 61: 3373-3381.
30. Huang S, Shu L, Dilling MB, Easton J, Harwood FC, Ichijo H et al. (2003). Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1). Mol Cell 11: 1491-1501.
31. Inoki K, Zhu T, Guan KL. (2003). TSC2 mediates cellular energy response to control cell growth and survival. Cell 115: 577-590.
32. Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y, Kondo S. (2004). Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ 11: 448-457.
33. Kim WY, Kaelin WG. (2004). Role of VHL gene mutation in human cancer. J Clin Oncol 22: 4991-5004.
34. Kwiatkowski DJ. (2003). Tuberous sclerosis: from tubers to mTOR. Ann Human Genet 67: 87-96.
35. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J et al. (1994). A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367: 645-648.
36. Law BK, Chytil A, Dumont N, Hamilton EG, Waltner-Law ME, Aakre ME et al. (2002). Rapamycin potentiates transforming growth factor beta-induced growth arrest in nontransformed, oncogene-transformed, and human cancer cells. Mol Cell Biol 22: 8184-8198.
37. Levine B, Klionsky DJ. (2004). Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 6: 463-477.
38. Li BD, Gruner JS, Abreo F, Johnson LW, Yu H, Nawas S et al. (2002). Prospective study of eukaryotic initiation factor 4E protein elevation and breast cancer outcome. Ann Surg 235: 732-738.
39. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI et al. (1997). PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943-1947.
40. Li SY, Rong M, Grieu F, Iacopetta B. (2006). PIK3CA mutations in breast cancer are associated with poor outcome. Breast Cancer Res Treat 96: 91-95.
41. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H et al. (1999). Induction of autophagy and inhibition of tumorigenesis by beclin. Nature 402: 672-676.
42. Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G et al. (1998). Protection against fatal sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol 72: 8586-8596.
43. Lieberthal W, Fuhro R, Andry CC, Rennke H, Abernathy VE, Koh JS et al. (2001). Rapamycin impairs recovery fromacute renal failure: role of cell-cycle arrest and apoptosis of tubular cells. Am J Physiol Renal Physiol 281: F693-706.
44. Liu L, Cash TP, Jones RG, Keith B, Thompson CB, Simon MC. (2006). Hypoxia-induced energy stress regulates mRNA translation and cell growth. Mol Cell 21: 521-531.
45. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L et al. (2001). Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7: 1194-1201.
46. Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM et al. (2004). mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nat Med 10: 594-601.
47. Martin ME, Perez MI, Redondo C, Alvarez MI, Salinas M, Fando JL. (2000). 4E binding protein 1 expression is inversely correlated to the progression of gastrointestinal cancers. Int J Biochem Cell Biol 32: 633-642.
48. Mohi MG, Boulton C, Gu TL, Sternberg DW, Neuberg D, Griffin JD et al. (2004). Combination of rapamycin and protein tyrosine kinase (PTK) inhibitors for the treatment of leukemias caused by oncogenic PTKs. Proc Natl Acad Sci USA 101: 3130-3135.
49. Neshat MS, Mellinghoff IK, Tran C, Stiles B, Thomas G, Petersen R et al. (2001). Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci USA 98: 10314-10319.
50. Noda T, Ohsumi Y. (1998). Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 273: 3963-3966.
51. Nourse J, Firpo E, Flanagan WM, Coats S, Polyak K, Lee MH et al. (1994). Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. Nature 372: 570-573.
52. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D et al. (2006). mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66: 1500-1508.
53. Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E et al. (2001). A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res 61: 439-444.
54. Paglin S, Lee N-Y, Nakar C, Fitzgerald M, Plotkin J, Deuel B et al. (2005). Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 Cells. Cancer Res 65: 11061-11070.
55. Pattingre S, Tassa A, Qu X, Garuti R, Liang XH, Mizushima N et al. (2005). Bcl-2 antiapoptotic proteins inhibit beclin 1-dependent autophagy. Cell 122: 927-939.
56. Podsypanina K, Lee RT, Politis C, Hennessy I, Crane A, Puc J et al. (2001). An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc Natl Acad Sci USA 98: 10320-10325.
57. Raje N, Kumar S, Hideshima T, Ishitsuka K, Chauhan D, Mitsiades C et al. (2004). Combination of the mTOR inhibitor rapamycin and CC-5013 has synergistic activity in multiple myeloma. Blood 104: 4188-4193.
58. Risinger JI, Hayes AK, Berchuck A, Barrett JC. (1997). PTEN/MMAC1 mutations in endometrial cancers. Cancer Res 57: 4736-4738.
59. Rosenwald IB. (1996). Upregulated expression of the genes encoding translation initiation factors eIF-4E and eIF-2alpha in transformed cells. Cancer Lett 102: 113-123.
60. Rosenwald IB, Chen JJ, Wang S, Savas L, London IM, Pullman J. (1999). Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis. Oncogene 18: 2507-2517.
61. Ruggero D, Montanaro L, Ma L, Xu W, Londei P, Cordon-Cardo C et al. (2004). The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis. Nat Med 10: 484-486.
62. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S et al. (2004). High frequency of mutations of the PIK3CA gene in human cancers. Science 304: 554.
63. Sarbassov dos D, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF et al. (2006). Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 22: 159-168.
64. Scott PA, Smith K, Poulsom R, De Benedetti A, Bicknell R, Harris AL. (1998). Differential expression of vascular endothelial growth factor mRNA vs protein isoform expression in human breast cancer and relationship to eIF-4E. Br J Cancer 77: 2120-2128.
65. Secombe J, Pierce SB, Eisenman RN. (2004). Myc: a weapon of mass destruction. Cell 117: 153-156.
66. Shantz LM, Pegg AE. (1994). Overproduction of ornithine decarboxylase caused by relief of translational repression is associated with neoplastic transformation. Cancer Res 54: 2313-2316.
67. Shaw RJ, Bardeesy N, Manning BD, Lopez L, Kosmatka M, DePinho RA et al. (2004). The LKB1 tumor suppressor negatively regulates mTOR signaling. Cancer Cell 6: 91-99.
68. Shayesteh L, Lu Y, Kuo WL, Baldocchi R, Godfrey T, Collins C et al. (1999). PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 21: 99-102.
69. Shi Y, Sharma A, Wu H, Lichtenstein A, Gera J. (2005a). Cyclin D1 and c-myc internal ribosome entry site (IRES)-dependent translation is regulated by AKT activity and enhanced by rapamycin through a p38 MAPK- and ERK-dependent pathway. J Biol Chem 280: 10964-10973.
70. Shinohara ET, Cao C, Niermann K, Mu Y, Zeng F, Hallahan DE et al. (2005). Enhanced radiation damage of tumor vasculature by mTOR inhibitors. 24: 5414-5422.
71. Sorrells DL, Meschonat C, Black D, Li BD. (1999). Pattern of amplification and overexpression of the eukaryotic initiation factor 4E gene in solid tumor. J Surg Res 85: 37-42.
72. Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH et al. (1997). Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet 15: 356-362.
73. Stoneley M, Chappell SA, Jopling CL, Dickens M, MacFarlane M, Willis AE. (2000). c-Myc protein synthesis is initiated from the internal ribosome entry segment during apoptosis. Mol Cell Biol 20: 1162-1169.
74. Thimmaiah KN, Easton JB, Germain GS, Morton CL, Kamath S, Buolamwini JK et al. (2005). Identification of N10-substituted phenoxazines as potent and specific inhibitors of Akt signaling. J Biol Chem 280: 31924-31935.
75. Thomas GV, Tran C, Mellinghoff IK, Welsbie DS, Chan E, Fueger B et al. (2006). Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat Med 12: 122-127.
76. Treins C, Giorgetti-Peraldi S, Murdaca J, Semenza GL, Van Obberghen E. (2002). Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway. J Biol Chem 277: 27975-27981.
77. Wang S, Lloyd RV, Hutzler MJ, Rosenwald IB, Safran MS, Patwardhan NA et al. (2001). Expression of eukaryotic translation initiation factors 4E and 2alpha correlates with the progression of thyroid carcinoma. Thyroid 11: 1101-1107.
78. Weinstein IB. (2002). CANCER: Enhanced: addiction to oncogenes-the achilles heal of cancer. Science 297: 63-64.
79. Wendel HG, De Stanchina E, Fridman JS, Malina A, Ray S, Kogan S et al. (2004). Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature 428: 332-337.
80. Witzig TE, Geyer SM, Ghobrial I, Inwards DJ, Fonseca R, Kurtin P et al. (2005). Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 23: 5347-5356.
81. Woltman AM, van der Kooij SW, Coffer PJ, Offringa R, Daha MR, van Kooten C. (2003). Rapamycin specifically interferes with GM-CSF signaling in human dendritic cells, leading to apoptosis via increased p27KIP1 expression. Blood 101: 1439-1445.
82. Wong AS, Kim SO, Leung PC, Auersperg N, Pelech SL. (2001). Profiling of protein kinases in the neoplastic transformation of human ovarian surface epithelium. Gynecol Oncol 82: 305-311.
83. Wu H, Yang J-M, Jin S, Zhang H, Hait WN. (2006). Elongation factor-2 kinase regulates autophagy in human glioblastoma cells. Cancer Res 66: 3015-3023.
84. Yan H, Frost P, Shi Y, Hoang B, Sharma S, Fisher M et al. (2006). Mechanism by which mammalian target of rapamycin inhibitors sensitize multiple myeloma cells to dexamethasone-induced apoptosis. Cancer Res 66: 2305-2313.
85. Yeung RS, Xiao G, Jin F, Lee W, Testa JR, Knudson AG. (1994). Predisposition to renal carcinoma in the eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2). Proc Natl Acad Sci USA 91: 11413-11416.
86. Yilmaz ñH, Valdez R, Theisen BK, Guo W, Ferguson DO, Wu H et al. (2006). Pten dependence distinguishes haematopoietic stem cells fromleukaemia-initiating cells. Nature 441: 475-478.
87. Yue Z, Jin S, Yang C, Levine AJ, Heintz N. (2003). Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA 100: 15077-15082.
88. Zha J, Harada H, Yang E, Jockel J, Korsmeyer SJ. (1996). Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L). Cell 87: 619-628.