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F1000Res. 2016 Aug 25;5. doi: 10.12688/f1000research.9207.1. eCollection 2016.

mTOR inhibitors in cancer therapy.

F1000Research

Jianling Xie, Xuemin Wang, Christopher G Proud

Affiliations

  1. Nutrition and Metabolism, South Australian Health and Medical research Institute, Adelaide, SA, Australia.
  2. Nutrition and Metabolism, South Australian Health and Medical research Institute, Adelaide, SA, Australia; School of Biological Sciences, University of Adelaide, Adelaide, SA, Australia.

PMID: 27635236 PMCID: PMC5007757 DOI: 10.12688/f1000research.9207.1

Abstract

The mammalian target of rapamycin, mTOR, plays key roles in cell growth and proliferation, acting at the catalytic subunit of two protein kinase complexes: mTOR complexes 1 and 2 (mTORC1/2). mTORC1 signaling is switched on by several oncogenic signaling pathways and is accordingly hyperactive in the majority of cancers. Inhibiting mTORC1 signaling has therefore attracted great attention as an anti-cancer therapy. However, progress in using inhibitors of mTOR signaling as therapeutic agents in oncology has been limited by a number of factors, including the fact that the classic mTOR inhibitor, rapamycin, inhibits only some of the effects of mTOR; the existence of several feedback loops; and the crucial importance of mTOR in normal physiology.

Keywords: cancer therapy; mTOR; mTOR inhibitors; rapamycin

Conflict of interest statement

The authors declare that they have no competing interests. No competing interests were disclosed. No competing interests were disclosed. No competing interests were disclosed.

References

  1. Mol Cell. 2010 Jun 11;38(5):768-74 - PubMed
  2. Cell Res. 2016 Mar;26(3):267-8 - PubMed
  3. Diabetes. 2003 Nov;52(11):2731-9 - PubMed
  4. Biochem Soc Trans. 2011 Apr;39(2):446-50 - PubMed
  5. Leukemia. 2012 Jun;26(6):1195-202 - PubMed
  6. Mol Cancer Ther. 2014 May;13(5):1078-91 - PubMed
  7. Transplantation. 1997 Jul 15;64(1):36-42 - PubMed
  8. J Biol Chem. 2009 Mar 20;284(12):8023-32 - PubMed
  9. Acta Pharmacol Sin. 2016 Mar;37(3):285-94 - PubMed
  10. Cancer Discov. 2016 Jan;6(1):59-70 - PubMed
  11. Hum Mol Genet. 2009 Sep 1;18(17):3298-310 - PubMed
  12. Diabetes. 2006 Sep;55(9):2429-36 - PubMed
  13. Cell Metab. 2016 Jun 14;23(6):990-1003 - PubMed
  14. Mol Cell. 2006 Apr 21;22(2):159-68 - PubMed
  15. Cancer Res. 2009 Aug 1;69(15):6232-40 - PubMed
  16. Cancer Res. 2010 Jan 1;70(1):288-98 - PubMed
  17. Nat Rev Cancer. 2011 May;11(5):325-37 - PubMed
  18. Proc Natl Acad Sci U S A. 2008 Nov 11;105(45):17414-9 - PubMed
  19. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5950-3 - PubMed
  20. Cancer Discov. 2014 May;4(5):546-53 - PubMed
  21. Nature. 2012 Feb 22;485(7396):55-61 - PubMed
  22. Science. 2005 Feb 18;307(5712):1098-101 - PubMed
  23. Biochem J. 2009 Jun 12;421(1):29-42 - PubMed
  24. Clin Cancer Res. 2010 Dec 15;16(24):6029-39 - PubMed
  25. Oncogene. 2010 May 6;29(18):2746-52 - PubMed
  26. Nucleic Acids Res. 2011 Jan;39(Database issue):D945-50 - PubMed
  27. Bioorg Med Chem Lett. 2013 Mar 1;23(5):1212-6 - PubMed
  28. J Antibiot (Tokyo). 1978 Jun;31(6):539-45 - PubMed
  29. Nat Rev Mol Cell Biol. 2014 Mar;15(3):155-62 - PubMed
  30. Trends Biochem Sci. 2016 Jun;41(6):532-45 - PubMed
  31. Transplantation. 1997 Jul 15;64(1):32-5 - PubMed
  32. Nat Rev Mol Cell Biol. 2011 Jan;12(1):21-35 - PubMed
  33. J Clin Invest. 2015 Jan;125(1):25-32 - PubMed
  34. Cancer Res. 2001 Feb 15;61(4):1527-32 - PubMed
  35. Nat Chem Biol. 2008 Nov;4(11):691-9 - PubMed
  36. Translation (Austin). 2014 Feb 14;2(1):e28174 - PubMed
  37. Semin Cell Dev Biol. 2014 Dec;36:113-20 - PubMed
  38. Science. 2016 Jan 1;351(6268):48-52 - PubMed
  39. Nat Med. 2008 Dec;14(12):1351-6 - PubMed
  40. J Antibiot (Tokyo). 1975 Oct;28(10):727-32 - PubMed
  41. Biochem Soc Trans. 2015 Oct;43(5):763-72 - PubMed
  42. Nature. 2016 May 18;534(7606):272-6 - PubMed
  43. Cancer Discov. 2011 Aug;1(3):248-59 - PubMed
  44. Biochem J. 2012 Jan 15;441(2):553-69 - PubMed
  45. Mol Cell Biol. 2003 Dec;23(23):8862-77 - PubMed
  46. Mol Cancer Ther. 2008 Jul;7(7):1851-63 - PubMed
  47. Oncogene. 2009 Mar 5;28(9):1187-96 - PubMed
  48. Cancer Discov. 2015 Nov;5(11):1127-9 - PubMed
  49. Cancer Res. 2013 Apr 15;73(8):2574-86 - PubMed
  50. J Antibiot (Tokyo). 1975 Oct;28(10):721-6 - PubMed
  51. Cancer Res. 2012 Dec 15;72(24):6468-76 - PubMed
  52. N Engl J Med. 2000 Jul 27;343(4):230-8 - PubMed
  53. Diabetes. 2005 Jul;54(7):2060-9 - PubMed
  54. Mol Cell Biol. 2010 Feb;30(4):908-21 - PubMed
  55. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12469-74 - PubMed
  56. Nat Rev Mol Cell Biol. 2013 Mar;14(3):133-9 - PubMed
  57. Mol Cancer Ther. 2009 Jul;8(7):1725-38 - PubMed
  58. J Antibiot (Tokyo). 1979 Jun;32(6):630-45 - PubMed
  59. Cell Signal. 2011 Oct;23(10):1515-27 - PubMed
  60. Cell Rep. 2015 Aug 11;12(6):937-43 - PubMed
  61. Cancer Cell. 2010 Mar 16;17(3):249-61 - PubMed
  62. J Biol Chem. 2011 Nov 18;286(46):40002-12 - PubMed
  63. PLoS One. 2013 Nov 18;8(11):e81669 - PubMed
  64. Cell Metab. 2013 Jun 4;17(6):1009-20 - PubMed
  65. Science. 2010 May 28;328(5982):1172-6 - PubMed
  66. EMBO J. 1998 Nov 16;17(22):6649-59 - PubMed
  67. Cell. 2007 Jan 26;128(2):257-67 - PubMed
  68. Cancer Cell. 2012 Jul 10;22(1):51-65 - PubMed
  69. Science. 1999 Sep 24;285(5436):2126-9 - PubMed
  70. Oncogene. 2014 Jan 23;33(4):474-83 - PubMed
  71. Science. 1997 Jul 4;277(5322):99-101 - PubMed
  72. Diabetologia. 2012 May;55(5):1355-65 - PubMed
  73. Cancer Discov. 2014 May;4(5):554-63 - PubMed
  74. Cancer Res. 2008 Jan 1;68(1):206-15 - PubMed
  75. Cell Metab. 2014 Mar 4;19(3):373-9 - PubMed
  76. Oncotarget. 2015 Jul 20;6(20):17895-910 - PubMed
  77. Biochem Soc Trans. 2009 Feb;37(Pt 1):227-31 - PubMed
  78. Nat Rev Dis Primers. 2016 May 26;2:16035 - PubMed
  79. PLoS Biol. 2009 Feb 10;7(2):e38 - PubMed
  80. ACS Med Chem Lett. 2010 Jan 19;1(1):39-43 - PubMed
  81. Autophagy. 2009 Jul;5(5):725-6 - PubMed
  82. Biochem Soc Trans. 2012 Feb;40(1):168-72 - PubMed

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