Skip to main content
SpringerLink
Log in

Proteasome Inhibitors as Therapy in Multiple Myeloma

  • Chapter
Myeloma Therapy

Part of the book series: Contemporary Hematology ((CH))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Rock K, Gramm C, Rothstein L, et al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 1994;78(5):761–71.

    Article  PubMed  CAS  Google Scholar 

  2. Goldberg AL. Protein degradation and protection against misfolded or damaged proteins. Nature 2003;426(6968):895–9.

    Article  PubMed  CAS  Google Scholar 

  3. Goldberg AL. Functions of the proteasome: from protein degradation and immune surveillance to cancer therapy. Biochem Soc Trans 2007;35(Pt. 1):12–7.

    Article  PubMed  CAS  Google Scholar 

  4. Adams J. The proteasome: a suitable antineoplastic target. Nat Rev Cancer 2004;4(5):349–60.

    Article  PubMed  CAS  Google Scholar 

  5. Ciechanover A, Elias S, Heller H, Ferber S, Hershko A. Characterization of the heat-stable polypeptide of the ATP-dependent proteolytic system from reticulo-cytes. J Biol Chem 1980;255(16):7525–8.

    PubMed  CAS  Google Scholar 

  6. Ciechanover A, Finley D, Varshavsky A. The ubiquitin-mediated proteolytic pathway and mechanisms of energy-dependent intracellular protein degradation. J Cell Biochem 1984;24(1):27–53.

    Article  PubMed  CAS  Google Scholar 

  7. Ciechanover A, Heller H, Elias S, Haas AL, Hershko A. ATP-dependent conjugation of reticulocyte proteins with the polypeptide required for protein degradation. Proc Natl Acad Sci U S A 1980;77(3):1365–8.

    Article  PubMed  CAS  Google Scholar 

  8. Ciechanover A, Schwartz AL. The ubiquitin-proteasome pathway: the complexity and myriad functions of proteins death. Proc Natl Acad Sci U S A 1998;95(6):2727–30.

    Article  PubMed  CAS  Google Scholar 

  9. Ciehanover A, Hod Y, Hershko A. A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. Biochem Biophys Res Commun 1978;81(4):1100–5.

    Article  PubMed  CAS  Google Scholar 

  10. Hershko A, Ciechanover A, Heller H, Haas AL, Rose IA. Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis. Proc Natl Acad Sci U S A 1980;77(4):1783–6.

    Article  PubMed  CAS  Google Scholar 

  11. Hershko A, Ciechanover A. Mechanisms of intracellular protein breakdown. Annu Rev Biochem 1982;51:335–64.

    Article  PubMed  CAS  Google Scholar 

  12. Wilk S, Orlowski M Evidence that pituitary cation-sensitive neutral endopeptidase is a multicatalytic protease complex. J Neurochem 1983;40(3):842–9.

    Article  PubMed  CAS  Google Scholar 

  13. Hough R, Pratt G, Rechsteiner M. Purification of two high molecular weight proteases from rabbit reticulocyte lysate. J Biol Chem 1987;262(17):8303–13.

    PubMed  CAS  Google Scholar 

  14. Waxman L, Fagan JM, Goldberg AL. Demonstration of two distinct high molecular weight proteases in rabbit reticulocytes, one of which degrades ubiquitin conjugates. J Biol Chem 1987;262(6):2451–7.

    PubMed  CAS  Google Scholar 

  15. Eytan E, Ganoth D, Armon T, Hershko A. ATP-dependent incorporation of 20S protease into the 26S complex that degrades proteins conjugated to ubiquitin. Proc Natl Acad Sci U S A 1989;86(20):7751–5.

    Article  PubMed  CAS  Google Scholar 

  16. Ganoth D, Leshinsky E, Eytan E, Hershko A. A multicomponent system that degrades proteins conjugated to ubiquitin. Resolution of factors and evidence for ATP-dependent complex formation. J Biol Chem 1988;263(25):12412–9.

    PubMed  CAS  Google Scholar 

  17. Arrigo A-P, Suhan JP, Welch WJ. Dynamic changes in the structure and intracel-lular locale of the mammalian low-molecular-weight heat shock protein. Mol Cell Biol 1988;8:5059–71.

    PubMed  CAS  Google Scholar 

  18. Arrigo AP, Tanaka K, Goldberg AL, Welch WJ. Identity of the 19S ‘prosome’ particle with the large multifunctional protease complex of mammalian cells (the proteasome). Nature 1988;331(6152):192–4.

    Article  PubMed  CAS  Google Scholar 

  19. Peters J, Franke W, Kleinschmidt J. Distinct 19 S and 20 S subcomplexes of the 26 S proteasome and their distribution in the nucleus and the cytoplasm. J Biol Chem 1994;269(10):7709–18.

    PubMed  CAS  Google Scholar 

  20. Gray C, Slaughter C, DeMartino G. PA28 activator protein forms regulatory caps on proteasome stacked rings. J Mol Biol 1994;236(1):7–15.

    Article  PubMed  CAS  Google Scholar 

  21. Hershko A. The ubiquitin system for protein degradation and some of its roles in the control of the cell division cycle. Cell Death Differ 2005;12(9):1191–7.

    Article  PubMed  CAS  Google Scholar 

  22. Hershko A, Heller H, Elias S, Ciechanover A. Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J Biol Chem 1983;258(13):8206–14.

    PubMed  CAS  Google Scholar 

  23. Wilkinson K, Urban M, Haas A. Ubiquitin is the ATP-dependent proteolysis factor I of rabbit reticulocytes. J Biol Chem 1980;255(16):7529–32.

    PubMed  CAS  Google Scholar 

  24. Hough R, Pratt G, Rechsteiner M. Ubiquitin-lysozyme conjugates. Identification and characterization of an ATP-dependent protease from rabbit reticulocyte lysates. J Biol Chem 1986;261(5):2400–8.

    PubMed  CAS  Google Scholar 

  25. Swaminathan S, Amerik A, Hochstrasser M. The Doa4 deubiquitinating enzyme is required for ubiquitin homeostasis in yeast. Mol Biol Cell 1999;10(8):2583–94.

    PubMed  CAS  Google Scholar 

  26. Pickart CM. Back to the future with ubiquitin. Cell 2004;116(2):181–90.

    Article  PubMed  CAS  Google Scholar 

  27. Arendt C, Hochstrasser M. Identification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation. Proc Natl Acad Sci U S A 1997;94(14):7156–61.

    Article  PubMed  CAS  Google Scholar 

  28. Heinemeyer W, Fischer M, Krimmer T, Stachon U, Wolf D. The active sites of the eukaryotic 20 S proteasome and their involvement in subunit precursor processing. J Biol Chem 1997;272(40):25200–9.

    Article  PubMed  CAS  Google Scholar 

  29. Kisselev AF, Callard A, Goldberg AL. Importance of the different proteolytic sites of the proteasome and the efficacy of inhibitors varies with the protein substrate. J Biol Chem 2006;281(13):8582–90.

    Article  PubMed  CAS  Google Scholar 

  30. Kisselev AF, Goldberg AL. Proteasome inhibitors: from research tools to drug candidates. Chem Biol 2001;8(8):739–58.

    Article  PubMed  CAS  Google Scholar 

  31. Glotzer M, Murray A, Kirschner M. Cyclin is degraded by the ubiquitin pathway. Nature 1991;349(6305):132–8.

    Article  PubMed  CAS  Google Scholar 

  32. Pagano M, Tam S, Theodoras A, et al. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 1995;269(5224):682–5.

    Article  PubMed  CAS  Google Scholar 

  33. Zhao J, Tenev T, Martins L, Downward J, Lemoine N. The ubiquitin-proteasome pathway regulates survivin degradation in a cell cycle-dependent manner. J Cell Sci 2000;113(Pt. 23):4363–71.

    PubMed  CAS  Google Scholar 

  34. Finley D, Sadis S, Monia B, et al. Inhibition of proteolysis and cell cycle progression in a multiubiquitination-deficient yeast mutant. Mol Cell Biol 1994;14(8):5501–9.

    PubMed  CAS  Google Scholar 

  35. Adams J, Palombella VJ, Sausville EA, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 1999;59(11):2615–22.

    PubMed  CAS  Google Scholar 

  36. Dantuma N, Lindsten K, Glas R, Jellne M, Masucci M. Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells. Nat Biotechnol 2000;18(5):538–43.

    Article  PubMed  CAS  Google Scholar 

  37. Masdehors P, Omura S, Merle-Beral H, et al. Increased sensitivity of CLL-derived lymphocytes to apoptotic death activation by the proteasome-specific inhibitor lactacystin. Br J Haematol 1999;105(3):752–7.

    Article  PubMed  CAS  Google Scholar 

  38. Drexler HC, Risau W, Konerding MA. Inhibition of proteasome function induces programmed cell death in proliferating endothelial cells. Faseb J 2000;14(1):65–77.

    PubMed  CAS  Google Scholar 

  39. Kudo Y, Takata T, Ogawa I, et al. p27Kip1 accumulation by inhibition of proteas-ome function induces apoptosis in oral squamous cell carcinoma cells. Clin Cancer Res 2000;6(3):916–23.

    PubMed  CAS  Google Scholar 

  40. Bogner C, Schneller F, Hipp S, Ringshausen I, Peschel C, Decker T. Cycling B-CLL cells are highly susceptible to inhibition of the proteasome: involvement of p27, early D-type cyclins, Bax, and caspase-dependent and -independent pathways. Exp Hematol 2003;31(3):218–25.

    Article  PubMed  CAS  Google Scholar 

  41. Hideshima T, Richardson P, Chauhan D, et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 2001;61(7):3071–6.

    PubMed  CAS  Google Scholar 

  42. Chauhan D, Catley L, Li G, et al. A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib. Cancer Cell 2005;8(5):407–19.

    Article  PubMed  CAS  Google Scholar 

  43. Adams J. Potential for proteasome inhibition in the treatment of cancer. Drug Discov Today 2003;8(7):307–15.

    Article  PubMed  CAS  Google Scholar 

  44. Chauhan D, Hideshima T, Anderson KC. Proteasome inhibition in multiple myeloma: therapeutic implication. Annu Rev Pharmacol Toxicol 2005;45:465–76.

    Article  PubMed  CAS  Google Scholar 

  45. Chauhan D, Hideshima T, Mitsiades C, Richardson P, Anderson KC. Proteasome inhibitor therapy in multiple myeloma. Mol Cancer Ther 2005;4(4):686–92.

    Article  PubMed  CAS  Google Scholar 

  46. Vinitsky A, Michaud C, Powers JC, Orlowski M. Inhibition of the chymotrypsin-like activity of the pituitary multicatalytic proteinase complex. Biochemistry 1992 ; 31 (39) : 9421–8.

    Article  PubMed  CAS  Google Scholar 

  47. Omura S, Fujimoto T, Otoguro K, et al. Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells. J Antibiot (Tokyo) 1991;44(1):113–6.

    CAS  Google Scholar 

  48. Fenteany G, Standaert R, Lane W, Choi S, Corey E, Schreiber S. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science 1995;268(5211):726–31.

    Article  PubMed  CAS  Google Scholar 

  49. Fenteany G, Standaert R, Reichard G, Corey E, Schreiber S. A beta-lactone related to lactacystin induces neurite outgrowth in a neuroblastoma cell line and inhibits cell cycle progression in an osteosarcoma cell line. Proc Natl Acad Sci U S A 1994;91(8):3358–62.

    Article  PubMed  CAS  Google Scholar 

  50. Adams J, Kauffman M. Development of the proteasome inhibitor Velcade (Bortezomib). Cancer Invest 2004;22(2):304–11.

    Article  PubMed  CAS  Google Scholar 

  51. Karin M, Yamamoto Y, Wang QM. The IKK NF-kappa B system: a treasure trove for drug development. Nat Rev Drug Discov 2004;3(1):17–26.

    Article  PubMed  CAS  Google Scholar 

  52. Van WC. Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res 2007;13(4):1076–82.

    Article  Google Scholar 

  53. Stancovski I, Baltimore D. NF-κ B activation: the I κB kinase revealed? Cell 1997;91:299–302.

    Article  PubMed  CAS  Google Scholar 

  54. Haefner B. NF-kappa B: arresting a major culprit in cancer. Drug Discov Today 2002;7(12):653–63.

    Article  PubMed  CAS  Google Scholar 

  55. Palombella VJ, Rando OJ, Goldberg AL, Maniatis T. The ubiquitin proteasome pathway is required for processing the NF-kB1 precursor protein and the activation of NF-kB. Cell 1994;78:773–85.

    Article  PubMed  CAS  Google Scholar 

  56. Jensen TJ, Loo MA, Pind S, Williams DB, Goldberg AL, Riordan JR. Multiple proteolytic systems, including the proteasome, contribute to CFTR processing. Cell 1995;83(1):129–35.

    Article  PubMed  CAS  Google Scholar 

  57. Chauhan D, Uchiyama H, Urashima M, Yamamoto K, Anderson KC. Regulation of interleukin 6 in multiple myeloma and bone marrow stromal cells. Stem Cells 1995;13(Suppl 2):35–9.

    PubMed  CAS  Google Scholar 

  58. Chauhan D, Uchiyama H, Akbarali Y, et al. Multiple myeloma cell adhesion-induced interleukin-6 expression in bone marrow stromal cells involves activation of NF-kappa B. Blood 1996;87(3):1104–12.

    PubMed  CAS  Google Scholar 

  59. Ni H, Ergin M, Huang Q, et al. Analysis of expression of nuclear factor kappa B (NF-kappa B) in multiple myeloma: downregulation of NF-kappa B induces apop-tosis. Br J Haematol 2001;115(2):279–86.

    Article  PubMed  CAS  Google Scholar 

  60. Mitsiades N, Mitsiades CS, Poulaki V, et al. Biologic sequelae of nuclear factor-kappaB blockade in multiple myeloma: therapeutic applications. Blood 2002;99(11):4079–86.

    Article  PubMed  CAS  Google Scholar 

  61. Landowski TH, Olashaw NE, Agrawal D, Dalton WS. Cell adhesion-mediated drug resistance (CAM-DR) is associated with activation of NF-kappa B (RelB/p50) in myeloma cells. Oncogene 2003;22(16):2417–21.

    Article  PubMed  CAS  Google Scholar 

  62. Bharti AC, Donato N, Singh S, Aggarwal BB. Curcumin (diferuloylmethane) down-regulates the constitutive activation of nuclear factor-kappa B and Ikappa Balpha kinase in human multiple myeloma cells, leading to suppression of proliferation and induction of apoptosis. Blood 2003;101(3):1053–62.

    Article  PubMed  CAS  Google Scholar 

  63. LeBlanc R, Catley LP, Hideshima T, et al. Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and prolongs survival in a murine model. Cancer Res 2002;62(17):4996–5000.

    PubMed  CAS  Google Scholar 

  64. Orlowski RZ, Stinchcombe TE, Mitchell BS, et al. Phase I trial of the proteasome inhibitor PS-341 in patients with refractory hematologic malignancies. J Clin Oncol 2002;20(22):4420–7.

    Article  PubMed  CAS  Google Scholar 

  65. Richardson P, Blood E, Mitsiades CS, et al. A randomized phase 2 trial of lena-lidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006;15:3458–64.

    Article  CAS  Google Scholar 

  66. Richardson PG, Barlogie B, Berenson J, et al. Extended follow-up of a phase II trial in relapsed, refractory multiple myeloma: final time-to-event results from the SUMMIT trial. Cancer 2006;106(6):1316–9.

    Article  PubMed  CAS  Google Scholar 

  67. Jagannath S, Durie B, Wolf JL, et al. A phase 2 study of Bortezomib as first line therapy in patients with multiple myeloma. Blood 2004;104:abstr 333.

    Google Scholar 

  68. Jagannath S, Barlogie B, Berenson J, et al. A phase 2 study of two doses of bort-ezomib in relapsed or refractory myeloma. Br J Haematol 2004;127(2):165–72.

    Article  PubMed  CAS  Google Scholar 

  69. Jagannath S, Barlogie B, Berenson JR, et al. Bortezomib in recurrent and/or refractory multiple myeloma: initial experience in patients with impaired renal function. Cancer 2005;103:1195–200.

    Article  PubMed  CAS  Google Scholar 

  70. RichardsonPG,SonneveldP,SchusterMW,et al.Bortezomiborhigh-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005;352(24):2487–98.

    Article  PubMed  CAS  Google Scholar 

  71. Richardson P, Barlogie B, Berenson JR, et al. Clinical factors predictive of outcome with Bortezomib in patients with relapsed, refractory multiple myeloma. Blood 2005;106:2977–81.

    Article  PubMed  CAS  Google Scholar 

  72. Berenson J, Jagannath S, Barlogie B, et al. Safety of prolonged therapy with Bortezomib in relapsed or refractory multiple myeloma. Cancer 2005;104:2141–8.

    Article  PubMed  CAS  Google Scholar 

  73. Lonial S, Waller EK, Richardson P, et al. Risk factors and kinetics of thrombocyto-penia associated with bortezomib for relapsed, refractory multiple myeloma. Blood 2005;106:3777–84.

    Article  PubMed  CAS  Google Scholar 

  74. Richardson PG, Briemberg H Jagannath S, et al. Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 2006;24(19):3113–20.

    Article  PubMed  CAS  Google Scholar 

  75. Richardson PG, Hideshima T, Mitsiades C, Anderson KC. The emerging role of novel therapies for the treatment of relapsed myeloma. J Natl Compr Canc Netw 2007;5(2):149–62.

    PubMed  CAS  Google Scholar 

  76. Richardson PG, Sonneveld P, Schuster M, et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 2007;110(10):3557–60.

    Article  PubMed  CAS  Google Scholar 

  77. Hideshima T, Chauhan D, Richardson P, et al. NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem 2002;28:28.

    Google Scholar 

  78. Mitsiades N, Mitsiades CS, Poulaki V, et al. Molecular sequelae of proteasome inhibition in human multiple myeloma cells. Proc Natl Acad Sci U S A 2002;99(22):14374–9.

    Article  PubMed  CAS  Google Scholar 

  79. Chauhan D, Li G, Shringarpure R, et al. Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells. Cancer Res 2003;63(19):6174–7.

    PubMed  CAS  Google Scholar 

  80. Chauhan D, Li G, Hideshima T, et al. JNK-dependent release of mitochondrial protein, Smac, during apoptosis in multiple myeloma (MM) cells. J Biol Chem 2003;278(20):17593–6.

    Article  PubMed  CAS  Google Scholar 

  81. Chauhan D, Guilan L, Sattler M, et al. Superoxide-dependent and independent mitochondrial signaling during apoptosis in multiple myeloma (MM) cells. Oncogene 2003;22(40):6296–300.

    Article  PubMed  CAS  Google Scholar 

  82. Chauhan D, Anderson KC. Mechanisms of cell death and survival in multiple myeloma (MM): therapeutic implications. Apoptosis 2003;8(4):337–43.

    Article  PubMed  CAS  Google Scholar 

  83. Mitsiades N, Mitsiades CS, Richardson PG, et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemothera-peutic agents: therapeutic applications. Blood 2003;101(6):2377–80.

    Article  PubMed  CAS  Google Scholar 

  84. Hideshima T, Anderson KC. Molecular mechanisms of novel therapeutic approaches for multiple myeloma. Nat Rev Cancer 2002;2(12):927–37.

    Article  PubMed  CAS  Google Scholar 

  85. Hideshima T, Mitsiades C, Akiyama M, et al. Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. Blood 2003;101(4):1530–4.

    Article  PubMed  CAS  Google Scholar 

  86. Obeng EA, Boise LH. Caspase-12 and caspase-4 are not required for cas-pase-dependent endoplasmic reticulum stress-induced apoptosis. J Biol Chem 2005;280(33):29578–87.

    Article  PubMed  CAS  Google Scholar 

  87. Obeng EA, Carlson LM, Gutman DM, Harrington WJ, Jr., Lee KP, Boise LH. Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood 2006;107(12):4907–16.

    Article  PubMed  CAS  Google Scholar 

  88. Nawrocki ST, Carew JS, Dunner K, Jr., et al. Bortezomib inhibits PKR-like endoplasmic reticulum (ER) kinase and induces apoptosis via ER stress in human pancreatic cancer cells. Cancer Res 2005;65(24):11510–9.

    Article  PubMed  CAS  Google Scholar 

  89. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002;2(9):647–56.

    Article  PubMed  CAS  Google Scholar 

  90. Chauhan D, Velankar M, Brahmandam M, et al. A novel Bcl-2/Bcl-X(L)/Bcl-w inhibitor ABT-737 as therapy in multiple myeloma. Oncogene 2007;26(16):2374–80.

    Article  PubMed  CAS  Google Scholar 

  91. Chauhan D, Neri P, Velankar M, et al. Targeting mitochondrial factor Smac/DIABLO as therapy for multiple myeloma (MM). Blood 2007;109(3):1220–7.

    Article  PubMed  CAS  Google Scholar 

  92. Mulligan G, Mitsiades C, Bryant B, et al. Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib. Blood 2007;109(8):3177–88.

    Article  PubMed  CAS  Google Scholar 

  93. Mitsiades CS, Mitsiades NS, McMullan CJ, et al. Antimyeloma activity of heat shock protein-90 inhibition. Blood 2006;107(3):1092–100.

    Article  PubMed  CAS  Google Scholar 

  94. Mitsiades N, Mitsiades CS, Poulaki V, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood 2002;99(12):4525–30.

    Article  PubMed  CAS  Google Scholar 

  95. Hideshima T, Bradner JE, Wong J, et al. Small-molecule inhibition of protea-some and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci U S A 2005;102(24):8567–72.

    Article  PubMed  CAS  Google Scholar 

  96. Catley L, Weisberg E, Kiziltepe T, et al. Aggresome induction by protea-some inhibitor bortezomib and {alpha}-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells. Blood 2006;108(10):3441–9.

    Article  PubMed  CAS  Google Scholar 

  97. Nawrocki ST, Carew JS, Pino MS, et al. Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells. Cancer Res 2006;66(7):3773–81.

    Article  PubMed  CAS  Google Scholar 

  98. Munshi NC, Hideshima T, Carrasco D, et al. Identification of genes modulated in multiple myeloma using genetically identical twin samples. Blood 2004;103(5):1799–806.

    Article  PubMed  CAS  Google Scholar 

  99. Berkers CR, Verdoes M, Lichtman E,. Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. Nat Methods 2005;2(5):357–62.

    Article  PubMed  CAS  Google Scholar 

  100. Altun M, Galardy P, Shringapure R, et al. Effects of PS 341 on the activity and composition of proteasomes in multiple myeloma cells. Cancer Res 2005 ; 65 : 7896–901.

    PubMed  CAS  Google Scholar 

  101. Feling RH, Buchanan GO, Mincer TJ, Kauffman CA, Jensen PR, Fenica l W Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel micro-bial source, a marine bacterium of the new genus salinospora. Angew Chem Int Ed Engl 2003;42(3):355–7.

    Article  PubMed  CAS  Google Scholar 

  102. Macherla VR, Mitchell SS, Manam RR, et al. Structure-activity relationship studies of salinosporamide A (NPI-0052), a novel marine derived proteasome inhibitor. J Med Chem 2005;48(11):3684–7.

    Article  PubMed  CAS  Google Scholar 

  103. Groll M, Huber R, Potts BC. Crystal structures of Salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of beta-lactone ring opening and a mechanism for irreversible binding. J Am Chem Soc 2006;128(15):5136–41.

    Article  PubMed  CAS  Google Scholar 

  104. Ruiz S, Krupnik Y, Keating M, Chandra J, Palladino M, McConkey D. The proteasome inhibitor NPI-0052 is a more effective inducer of apoptosis than bort-ezomib in lymphocytes from patients with chronic lymphocytic leukemia. Mol Cancer Ther 2006;5(7):1836–43.

    Article  PubMed  CAS  Google Scholar 

  105. Miller CP, Ban K, Dujka ME, et al. NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells. Blood 2007;110(1):267–77.

    Article  PubMed  CAS  Google Scholar 

  106. Oberdorf J, Carlson EJ, Skach WR. Redundancy of mammalian proteasome beta subunit function during endoplasmic reticulum associated degradation. Biochemistry 2001;40(44):13397–405.

    Article  PubMed  CAS  Google Scholar 

  107. Demo SD, Kirk CJ, Aujay MA, et al. Antitumor activity of PR-171, a novel irreversible inhibitor of the proteasome. Cancer Res 2007;67(13):6383–91.

    Article  PubMed  CAS  Google Scholar 

  108. Stapnes C, Doskeland AP, Hatfield K, et al. The proteasome inhibitors bortezomib and PR-171 have antiproliferative and proapoptotic effects on primary human acute myeloid leukaemia cells. Br J Haematol 2007;136(6):814–28.

    Article  PubMed  CAS  Google Scholar 

  109. Chauhan D, Hideshima T, Anderson KC. A novel proteasome inhibitor NPI-0052 as an anticancer therapy. Br J Cancer 2006;95(8):961–5.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This investigation was supported by NIH grants CA 50947, CA 78373, and CA10070; the Myeloma Research Fund; and LeBow Family Fund to Cure Myeloma.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Myeloma Research, Dana-Farber Cancer Institute, Boston, MA, USA

    Dharminder Chauhan

  2. Dana-Farber Cancer Institute, Boston, MA, USA

    Dharminder Ajita & Dharminder Singh

  3. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Kenneth Anderson

Authors
  1. Dharminder Chauhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dharminder Ajita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dharminder Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenneth Anderson
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Winship Cancer Institute, Emory University, B3307 Clifton Road, Atlanta, GA, 30322, USA

    Sagar Lonial MD

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Chauhan, D., Ajita, D., Singh, D., Anderson, K. (2008). Proteasome Inhibitors as Therapy in Multiple Myeloma. In: Lonial, S. (eds) Myeloma Therapy. Contemporary Hematology. Humana Press. https://doi.org/10.1007/978-1-59745-564-0_26

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-564-0_26

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-934115-82-4

  • Online ISBN: 978-1-59745-564-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation