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Targeting the Proteasome Pathway for the Treatment of Solid Tumors

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Resistance to Proteasome Inhibitors in Cancer

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT))

Abstract

The ubiquitin-proteasome system (UPS) is a highly complex protein network that maintains proteostasis and cell viability through the targeted and timely turnover of selected substrates. The proteasome serves as the catalytic core of the UPS to precisely recognize and efficiently execute the rapid ATP-dependent removal of ubiquitinated proteins. Small-molecule pharmacologic inhibitors exploit the pivotal role of the proteasome in cellular metabolism as a molecular vulnerability in cancer cells to promote the selective cytotoxicity of tumor cells. Proteasome inhibitors (PIs) have yielded durable clinically responses that dramatically improve the survival of patients diagnosed with the invariably fatal hematologic malignancy multiple myeloma (MM). Success of the PI bortezomib in the treatment of the hematologic malignancy MM has emerged as the standard of care and catapulted the UPS into a position of prominence as a model system in cancer biology and drug development. However, advancement of PIs to improve the treatment of patients with solid tumors has been far more challenging and less successful. Clinical assessment of second-generation PIs progresses as well as pharmacologics to intervene at other points within the UPS is being explored for both hematologic and solid tumors. Agents to target non-proteolytic activities associated with the proteasome are emerging as are agents to inhibit Ub-binding proteins. New approaches to unravel the UPS should advance its utilization as a drug development platform in mechanism-based anticancer strategies that include PIs as monotherapy or in synergistic combinations that improve the outcome of patients with solid tumors.

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Abbreviations

ATP:

Adenosine triphosphate

CP:

Catalytic particle

CR:

Complete response

Ct-L:

Chymotryptic-like

DLT:

Dose limiting toxicities

EGFR:

Epidermal growth factor receptor

ER:

Endoplasmic reticulum

FDA:

Federal Drug Administration

γ-IFN:

Gamma-interferon

IL:

Interleukin

IV:

Intravenous

GTP:

Guanosine triphosphate

kDA:

Kilodalton

MM:

Multiple myeloma

MTD:

Maximally tolerated dose

NCI:

National Cancer Institute

NF-κB:

Nuclear factor kappa B

NSCLC:

Non-small cell lung cancer

ORR:

Overall response rate

PI:

Proteasome inhibitor

RP:

Regulatory particle

RCC:

Renal cell carcinoma

TNF-α:

Tumor necrosis factor-α

Ub:

Ubiquitin

UPS:

Ubiquitin-proteasome system

UPR:

Unfolded protein response

US:

United States

VEGFR:

Vascular endothelial growth factor receptor

References

  1. Schoenheimer R (1942) The dynamic state of body constituents. Harvard University Press, Cambridge

    Google Scholar 

  2. Simpson MV (1953) The release of labeled amino acids from proteins in liver slices. J Biol Chem 201:143–54

    PubMed  CAS  Google Scholar 

  3. De Duve C, Gianetto R, Appelmans F, Wattiaux R (1953) Enzymic content of the mitochondria fraction. Nature 172:1143–44

    Article  Google Scholar 

  4. Ciechanover A, Hod Y, Hershko A (1978) A heat-stable polypeptide component of an ATP-dependent proteolytic system from reticulocytes. Biochem Biophys Res Commun 81:1100–05

    Article  Google Scholar 

  5. Ciechanover A (2005) From the lysosome to ubiquitin and the proteasome. Nat Rev Mol Cell Biol 6:79–86

    Article  PubMed  CAS  Google Scholar 

  6. Eytan E, Ganoth D, Armon T, Hershko A (1989) ATP-dependent incorporation of 20S protease into the 26S complex that degrades proteins conjugated to ubiquitin. Proc Natl Acad Sci U S A 86:7751–55

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Driscoll J, Goldberg AL (1990) The proteasome (multicatalytic protease) is a component of the 1500-kDa proteolytic complex which degrades ubiquitin-conjugated proteins. J Biol Chem 265:4789–92

    PubMed  CAS  Google Scholar 

  8. Brown MG, Driscoll J, Monaco JJ (1991) Structural and serological similarity of MHC-linked LMP and proteasome (multicatalytic proteinase) complexes. Nature 353:355–7

    Article  PubMed  CAS  Google Scholar 

  9. Driscoll J, Brown MG, Finley D, Monaco JJ (1993) MHC-linked LMP gene products specifically alter peptidase activities of the proteasome. Nature 365:262–4

    Article  PubMed  CAS  Google Scholar 

  10. Ciechanover A, Hershko A, Rose I. (2004) http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2004

  11. Chen D, Dou QP (2010) The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention. Curr Protein Pept Sci 11(6):459–70

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Orlowski RZ, Kuhn DJ (2008) Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res 1649–57

    Google Scholar 

  13. Nawrocki ST, Bruns CJ, Harbison MT et al (2002) Effects of the proteasome inhibitor PS-341 on apoptosis and angiogenesis in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther 1:1243–53

    PubMed  CAS  Google Scholar 

  14. Williams S, Pettaway C, Song R (2003) Differential effects of the proteasome inhibitor bortezomib on apoptosis and angiogenesis in human prostate tumor xenografts. Mol Cancer Ther 2:835–43

    PubMed  CAS  Google Scholar 

  15. Hideshima T, Richardson P, Chauhan D et al (2006) The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res 61:3071–6

    Google Scholar 

  16. Kupperman E, et al. Cancer Res. Phase II results of Study PX-171-007: a phase Ib/II study of carfilzomib (CFZ), a selective proteasome inhibitor, in patients with selected advanced metastatic solid tumors. ASCO. 2009; Abstract 3515

    Google Scholar 

  17. Development: ONX 0914 (PR-957). www.onyx-pharm.com/view.cfm/679/ONX-0914

  18. Rodler ET, Infante JR, Siu LL. First-in-human, phase I dose-escalation study of investigational drug MLN9708, a second-generation proteasome inhibitor, in advanced nonhematologic malignancies. J Clin Oncol 2010;28:15s (suppl; abstr 3071)

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Piva R, Ruggeri B, Williams M et al (2008) CEP-18770: a novel, orally active proteasome inhibitor with a tumor-selective pharmacologic profile competitive with bortezomib. Blood 111(5):2765–75

    Article  PubMed  CAS  Google Scholar 

  21. Dick LR, Fleming PE (2010) Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Discov Today 15:243–9

    Article  PubMed  CAS  Google Scholar 

  22. ClinicalTrials.gov. NCT00531284—Phase 1b/2 Study of Carfilzomib in relapsed solid tumors and multiple myeloma

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  24. Min CK, Lee SE, Yahng SA et al (2013) The impact of novel therapeutic agents before and after frontline autologous stem cell transplantation in patients with multiple myeloma. Blood Res 48(3):198–205

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Yaqub S, Ballester G, Ballester O (2013) Frontline Therapy for multiple myeloma: a concise review of the evidence based on randomized clinical trials. Cancer Invest 31(8):529–537

    Article  PubMed  CAS  Google Scholar 

  26. De la Puente P, Azab AK (2013) Contemporary drug therapies for multiple myeloma. Drugs Today (Barc) 49(9):563–73

    Article  Google Scholar 

  27. Parlati F, Lee SJ, Aujay M et al (2009) Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome. Blood 114:3439–3447

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  29. Huber EM, Basler M, Schwab R, Heinemeyer W, Kirk CJ, Groettrup M, Groll M (2012) Immuno- and constitutive proteasome crystal structures reveal differences in substrate and inhibitor specificity. Cell 148:727–738

    Article  PubMed  CAS  Google Scholar 

  30. Korteum KM, Stewart AK (2013) Carfilzomib. Blood 121:893–7

    Article  Google Scholar 

  31. Potts BC, Albitar MX, Anderson KC et al (2011) Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets 11(3):254–284

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Feling RH, Buchanan GO, Mincer TJ et al (2003) A highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus Salinospora. Angew Chem Int Ed Engl 42(3):355–7

    Article  PubMed  CAS  Google Scholar 

  33. Chen KF, Yeh PY, Hsu C et al (2009) Bortezomib overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells in part through the inhibition of the phosphatidylinositol 3-kinase/Akt pathway. J Biol Chem 284:11121–33

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  34. Mitsiades CS, McMillin D, Kotoula V (2006) Antitumor effects of the proteasome inhibitor bortezomib in medullary and anaplastic thyroid carcinoma cells in vitro. J Clin Endocrinol Metab 91:4013–21

    Article  PubMed  CAS  Google Scholar 

  35. Lioni M, Noma K, Snyder A et al (2008) Bortezomib induces apoptosis in esophageal squamous cell carcinoma cells through activation of the p38 mitogen-activated protein kinase pathway. Mol Cancer Ther 7(9):2866–75

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  36. Ooi MG, Hayden PJ, Kotoula V et al (2009) Interactions of the Hdm2/p53 and proteasome pathways may enhance the antitumor activity of bortezomib. Clin Cancer Res 15:7153–60

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Yu C, Friday BB, Lai JP et al (2006) Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways. Mol Cancer Ther 5:2378–87

    Article  PubMed  CAS  Google Scholar 

  38. Sunwoo JB, Chen Z, Dong G et al (2008) Novel proteasome inhibitor PS-341 inhibits activation of nuclear factor-kappa B, cell survival, tumor growth, and angiogenesis in squamous cell carcinoma. Clin Cancer Res 7:1419–28

    Google Scholar 

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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Canfield SE, Zhu K, Williams SA (2006) Bortezomib inhibits docetaxel-induced apoptosis via a p21-dependent mechanism in human prostate cancer cells. Mol Cancer Ther 5:2043–50

    Article  PubMed  CAS  Google Scholar 

  41. Wu J, Kaufman RJ (2006) From acute ER stress to physiological roles of the unfolded protein response. Cell Death Differ 13:374–84

    Article  PubMed  CAS  Google Scholar 

  42. Kardosh A et al (2008) Aggravated endoplasmic reticulum stress as a basis for enhanced glioblastoma cell killing by bortezomib in combination with celecoxib or its non-coxib analogue, 2,5-dimethyl-celecoxib. Cancer Res 68:843–51

    Article  PubMed  CAS  Google Scholar 

  43. Hill DS, Martin S, Armstrong JL (2009) Combining the endoplasmic reticulum stress-inducing agents bortezomib and fenretinide as a novel therapeutic strategy for metastatic melanoma. Clin Cancer Res 15:1192–8

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  44. Williamson MJ, Silva MD, Terkelsen J (2009) The relationship among tumor architecture, pharmacokinetics, pharmacodynamics, and efficacy of bortezomib in mouse xenograft models. Mol Cancer Ther 8:3234–43

    Article  PubMed  CAS  Google Scholar 

  45. Buac D, Shen M, Schmitt S et al (2013) From bortezomib to other inhibitors of the proteasome and beyond. Curr Pharm Des 19(22):4025–4038

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  46. Caravita T, De Fabritiis P, Palumbo A (2006) Bortezomib: efficacy comparisons in solid tumors and hematologic malignancies. Nat Clin Pract Oncol 3:374–87

    Article  PubMed  CAS  Google Scholar 

  47. Wright JJ (2010) Combination therapy of bortezomib with novel targeted agents: an emerging treatment strategy. Clin Cancer Res 16(16):4094–04

    Article  PubMed  CAS  Google Scholar 

  48. Milano A, Perri F, Caponigro F (2009) The ubiquitin-proteasome system as a molecular target in solid tumors: an update on bortezomib. Oncotargets Ther 2:171–8

    CAS  Google Scholar 

  49. Fowler N, Kahl BS, Lee P et al (2011) Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. J Clin Oncol 29(25):3389–95

    Article  PubMed  CAS  Google Scholar 

  50. Li TH, Ho L, Piperdi B et al (2010) Phase II study of the proteasome inhibitor bortezomib (PS-341, Velcade) in chemotherapy-naive patients with advanced stage non-small cell lung cancer (NSCLC)Lung. Cancer 68(1):89–93

    Google Scholar 

  51. Shah MA, Power DG, Kindler HL et al (2011) A multicenter, phase II study of Bortezomib (PS-341) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma. Invest New Drugs 29(6):1475–81

    Article  PubMed  CAS  Google Scholar 

  52. Jatoi A, Dakhil SR, Foster NR et al (2008) Bortezomib, paclitaxel, and carboplatin as a first-line regimen for patients with metastatic esophageal, gastric, and gastroesophageal cancer - Phase II Results from the North Central Cancer Treatment Group (N044B). J Thorac Oncol 3(5):516–20

    Article  PubMed  PubMed Central  Google Scholar 

  53. ClinicalTrials.gov. http://clinicaltrials.gov/show/NCT00923247

  54. Carlomagno F, Vitagliano D, Guida T et al (2002) ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res 62:7284–90

    PubMed  CAS  Google Scholar 

  55. Dubrey S, Schiller JH (2005) Three emerging new drugs for NSCLC: pemetrexed, bortezomib and cetuximab. Oncologist 10(4):282–291

    Article  Google Scholar 

  56. Hayslip J, Chaudhary U, Green M, Meyer M, Dunder S, Sherman C et al (2007) Bortezomib in combination with celecoxib in patients with advanced solid tumors: a phase I trial. BMC Cancer 7:221

    Article  PubMed  PubMed Central  Google Scholar 

  57. Kondagunta GV, Drucker B, Schwartz L et al (2004) Phase II trial of bortezomib for patients with advanced renal cell carcinoma. J Clin Oncol 22:3720–5

    Article  PubMed  CAS  Google Scholar 

  58. Davies AM, Lara PN, Lau DH et al (2004) The proteasome inhibitor, bortezomib, in combination with gemcitabine (Gem) and carboplatin (Carbo) in advanced non-small cell lung cancer (NSCLC): final results of a phase I California Cancer Consortium study. Proc Am Soc Clin Oncol 23:639a

    Google Scholar 

  59. Ryan DP, O’Neil B, Lima CR et al (2003) Phase I dose-escalation study of the proteasome inhibitor, bortezomib, plus irinotecan in patients with advanced solid tumors. Proc Am Soc Clin Oncol 22:228a

    Google Scholar 

  60. Erlichman C, Adjei AA, Thomas JPT et al (2001) A phase I trial of the proteasome inhibitor PS-341 in patients with advanced cancer. Proc Am Soc Clin Oncol 20:85a

    Google Scholar 

  61. Aghajanian C, Soignet S, Dizon D et al (2001) A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies. Proc Am Soc Clin Oncol 20:85a

    Google Scholar 

  62. Fanucchi MP, Belt RJ, Fossella FV et al (2004) Phase (ph) 2 study of bortezomib ± docetaxel in previously treated patients (pts) with advanced non-small cell lung cancer (NSCLC): preliminary results. Proc Am Soc Clin Oncol 23:640a

    Article  Google Scholar 

  63. Stevenson JP, Nho CW, Johnson SW et al (2004) Effects of bortezomib (PS-341) on NF-κΒ activation in peripheral blood mononuclear cells (PBMCs) of advanced non-small cell lung cancer (NSCLC) patients: a phase II/pharmacodynamic trial. Proc Am Soc Clin Oncol 23:649a

    Google Scholar 

  64. Rosen PJ, Gordon M, Lee PN. Phase II results of study PX-171-007: a phase Ib/II study of carfilzomib (CFZ), a selective proteasome inhibitor, in patients with selected advanced metastatic solid tumors. J Clin Oncol 2009;27:15s (suppl; abstr 3515)

    Google Scholar 

  65. Papadopoulos KP, Mendelson DS, Tolcher AW. A phase I, open-label, dose-escalation study of the novel oral proteasome inhibitor (PI) ONX 0912 in patients with advanced refractory or recurrent solid tumors, J Clin Oncol 2011;29: (suppl; abstr 3075)

    Google Scholar 

  66. Muchamuel T, Basler M, Aujay MA, Groettrup M (2009) A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat Med 15(7):781–7

    Article  PubMed  CAS  Google Scholar 

  67. Kumar SK, Jett J, Marks R, Richardson R, Quevedo F, Moynihan T, Croghan G, Adjei AA (2013) Phase 1 study of sorafenib in combination with bortezomib in patients with advanced malignancies. Invest New Drugs 31(5):1201–6

    Article  PubMed  CAS  Google Scholar 

  68. Gallerani E, Zucchetti M, Brunelli D et al (2013) A first in human phase I study of the proteasome inhibitor CEP-18770 in patients with advanced solid tumours and multiple myeloma. Eur J Cancer 49(2):290–6

    Article  PubMed  CAS  Google Scholar 

  69. Jones MD, Liu JC, Barthel TK, Hussain S, Lian JB (2010) A proteasome inhibitor, bortezomib, inhibits breast cancer growth and reduces osteolysis by downregulating metastatic genes. Clin Cancer Res 16(20):4978–4989

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  70. Finley D (2009) Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem 78:477–513

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  71. Husnjak K, Elsasser S, Zhang N, Chen X, Randles L, Shi Y et al (2008) Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature 453:481–8

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  72. Lee BH, Lee MJ, Park S, Oh DC, Elsasser S, Chen PC et al (2010) Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 467:179–84

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  73. Lee MJ, Lee BH, Hanna J, King RW, Finley D (2011) Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes. Mol Cell Proteomics 10:R110.003871

    Article  PubMed  PubMed Central  Google Scholar 

  74. D'Arcy P, Brnjic S, Olofsson MH et al (2011) Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat. Med, Epub

    Google Scholar 

  75. Fehlker M, Wendler P, Lehmann A, Enenkel C (2004) Blm3 is part of nascent proteasomes and is involved in a late stage of nuclear proteasome assembly. EMBO Rep 4:959–63

    Article  Google Scholar 

  76. Leggett DS, Hanna J, Borodovsky A et al (2002) Multiple associated proteins regulate proteasome structure and function. Mol Cell 10:495–507

    Article  PubMed  CAS  Google Scholar 

  77. Crosas B, Hanna J, Kirkpatrick DS et al (2006) Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities. Cell 127:1401–13

    Article  PubMed  CAS  Google Scholar 

  78. Ortolan TG, Tongaonkar P, Lambertson D et al (2000) The Rad23 DNA repair protein is a negative regulator of substrate-linked multi-ubiquitin chain assembly. Nat Cell Biol 2:601–8

    Article  PubMed  CAS  Google Scholar 

  79. Baird TD, Wek RC (2012) Eukaryotic initiation factor 2 phosphorylation and translational control in metabolism. Adv Nutr 3:307–321

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  80. Harding HP, Calfon M, Urano F, Novoa I, Ron D (2002) Transcriptional and translational control in the mammalian unfolded protein response. Annu Rev Cell Dev Biol 18:575–599

    Article  PubMed  CAS  Google Scholar 

  81. Zhu K, Dunner K Jr, McConkey DJ (2010) Proteasome inhibitors activate autophagy as a cytoprotective response in human prostate cancer cells. Oncogene 29:451–462

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  82. Trinh MA, Kaphzan H, Wek RC, Pierre P, Cavener DR, Klann E (2012) Brain-specific disruption of the eIF2T kinase PERK decreases ATF4 expression and impairs behavioral flexibility. Cell Rep 1:676–678

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  83. Hetz C, Chevet E, Harding HP (2013) Targeting the unfolded protein response in disease. Nat Rev Drug Discov 12:703–719

    Article  PubMed  CAS  Google Scholar 

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The authors disclose no conflicts of interest

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Authors and Affiliations

  1. Division of Hematology & Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

    Nisar Ahmad & Mohamed A. Y. Abdel Malek

  2. Division of Hematology & Oncology, Hematologic Malignancies and Bone Marrow Transplant, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

    Elias Anaissie & James J. Driscoll

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  1. Nisar Ahmad
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  2. Elias Anaissie
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  3. Mohamed A. Y. Abdel Malek
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  4. James J. Driscoll
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Correspondence to James J. Driscoll .

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  1. Wayne State University, Detroit, Michigan, USA

    Q. Ping Dou

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Ahmad, N., Anaissie, E., Malek, M.A.Y.A., Driscoll, J.J. (2014). Targeting the Proteasome Pathway for the Treatment of Solid Tumors. In: Dou, Q. (eds) Resistance to Proteasome Inhibitors in Cancer. Resistance to Targeted Anti-Cancer Therapeutics. Springer, Cham. https://doi.org/10.1007/978-3-319-06752-0_9

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