The proteasome as a target for cancer treatment: Focus on bortezomib

American Journal of Cancer

Volumn 4, Issue 6, 2005, Pages 359-372

  Papandreou, Christos N ^a,b  

^a UNIVERSITY OF TEXAS   (United States)

^b UNIVERSITY OF THESSALY   (Greece)

Author keywords

[No Author keywords available]

Indexed keywords

6 CHLORO 8 NICOTINAMIDO BETA CARBOLINE; 7 ETHYL 10 HYDROXYCAMPTOTHECIN; ADENOVIRUS VECTOR; BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; BORTEZOMIB; CATECHIN; DAUNORUBICIN; DIHYDROEPONEMYCIN; DOXORUBICIN; EPONEMYCIN; EPOXOMICIN; ESTRAMUSTINE; ETOPOSIDE; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; GLIOTOXIN; I KAPPA B KINASE INHIBITOR; IRINOTECAN; LACTACYSTIN; LOPERAMIDE; MITOMYCIN; PACLITAXEL; PEPTIDE DERIVATIVE; PEPTIDE HORMONE; PROTEASOME INHIBITOR; SYNTHETIC PEPTIDE; THALIDOMIDE; TMC 95A; UNCLASSIFIED DRUG; UNINDEXED DRUG; VINBLASTINE;

ABDOMINAL CRAMP; ABDOMINAL PAIN; ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; ANEMIA; APOPTOSIS; BREAST CARCINOMA; CANCER; CANCER CELL; CANCER THERAPY; CELL CYCLE REGULATION; CELL PROLIFERATION; CLINICAL TRIAL; COLORECTAL CARCINOMA; CONSTIPATION; DEHYDRATION; DIARRHEA; DRUG FATALITY; DRUG TOLERABILITY; ENZYME INHIBITION; FATIGUE; GASTROINTESTINAL DISEASE; HEMATOLOGIC MALIGNANCY; HUMAN; HYPOKALEMIA; HYPONATREMIA; HYPOTENSION; LEUKOPENIA; LYMPHOCYTOPENIA; MALAISE; MULTIPLE MYELOMA; MYALGIA; NEUROPATHY; NEUTROPENIA; NONHUMAN; ORTHOSTATIC HYPOTENSION; PANCREAS CANCER; PATHOPHYSIOLOGY; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PRIORITY JOURNAL; PROSTATE CARCINOMA; PROTEIN FUNCTION; PROTEIN STRUCTURE; PROTEIN TARGETING; RADICULOPATHY; REVIEW; SYNCOPE; THORAX PAIN; THROMBOCYTOPENIA; VOMITING;

EID: 29344447247     PISSN: 11756357     EISSN: 11756357     Source Type: Journal    
DOI: 10.2165/00024669-200504060-00003     Document Type: Review

References (152)

1. Adams J. The proteasome: structure, function, and role in the cell. Cancer Treat Rev 2003; 29 Suppl. 1: 3-9
2. King RW, Deshaies RJ, Peters JM, et al. How proteolysis drives the cell cycle. Science 1996; 274: 1652-9
3. Dahlmann B, Kopp F, Kuehn L, et al. The multicatalytic proteinase (prosome) is ubiquitous from eukaryotes to archaebacteria. FEBS Lett 1989; 251: 125-31
4. Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998; 67: 425-79
5. Eytan E, Ganoth D, Armon T, et al. 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: 7751-5
6. Zwickl P, Voges D, Baumeister W. The proteasome: a macromolecular assembly designed for controlled proteolysis. Philos Trans R Soc Lond B Biol Sci 1999; 354: 1501-11
7. Kisselev AF, Goldberg AL. Proteasome inhibitors: from research tools to drug candidates. Chem Biol 2001; 8: 739-58
8. Lupas A, Koster AJ, Baumeister W. Structural features of 26S and 20S proteasomes. Enzyme Protein 1993; 47: 252-73
9. Dick TP, Nussbaum AK, Deeg M, et al. Contribution of proteasomal beta-subunits to the cleavage of peptide substrates analyzed with yeast mutants. J Biol Chem 1998; 273: 25637-46
10. Nussbaum AK, Dick TP, Keilholz W, et al. Cleavage motifs of the yeast 20S proteasome beta subunits deduced from digests of enolase 1. Proc Natl Acad Sci U S A 1998; 95: 12504-9
11. Rock KL, 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: 761-71
12. Heinemeyer W, Fischer M, Krimmer T, et al. The active sites of the eukaryotic 20 S proteasome and their involvement in subunit precursor processing. J Biol Chem 1997; 272: 25200-9
13. Roth AF, Davis NG. Ubiquitination of the PEST-like endocytosis signal of the yeast a-factor receptor. J Biol Chem 2000; 275: 8143-53
14. Marchal C, Haguenauer-Tsapis R, Urban-Grimal D. A PEST-like sequence mediates phosphorylation and efficient ubiquitination of yeast uracil permease. Mol Cell Biol 1998; 18: 314-21
15. Lee PL, Midelfort CF, Murakami K, et al. Multiple forms of ubiquitin-protein ligase. Binding of activated ubiquitin to protein substrates. Biochemistry 1986; 25: 3134-8
16. Kisselev AF, Songyang Z, Goldberg AL. Why does threonine, and not serine, function as the active site nucleophile in proteasomes? J Biol Chem 2000; 275: 14831-7
17. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev 2002; 82: 373-428
18. Adams J, Behnke M, Chen S, et al. Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids. Bioorg Med Chem Lett 1998; 8: 333-8
19. Adams J. Proteasome inhibitors as new anticancer drugs. Curr Opin Oncol 2002; 14: 628-34
20. Orlowski M, Cardozo C, Michaud C. Evidence for the presence of five distinct proteolytic components in the pituitary multicatalytic proteinase complex: properties of two components cleaving bonds on the carboxyl side of branched chain and small neutral amino acids. Biochemistry 1993; 32: 1563-72
21. Palmer JT, Rasnick D, Klaus JL, et al. Vinyl sulfones as mechanism-based cysteine protease inhibitors. J Med Chem 1995; 38: 3193-6
22. Bogyo M, McMaster JS, Gaczynska M, et al. Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors. Proc Natl Acad Sci U S A 1997; 94: 6629-34
23. Dick LR, Cruikshank AA, Grenier L, et al. Mechanistic studies on the inactivation of the proteasome by lactacystin: a central role for clasto-lactacystin beta-lactone. J Biol Chem 1996; 271: 7273-6
24. Fenteany G, Standaert RF, Lane WS, et al. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science 1995; 268: 726-31
25. Ostrowska H, Wojcik C, Omura S, et al. Lactacystin, a specific inhibitor of the proteasome, inhibits human platelet lysosomal cathepsin A-like enzyme. Biochem Biophys Res Commun 1997; 234: 729-32
26. Geier E, Pfeifer G, Wilm M, et al. A giant protease with potential to substitute for some functions of the proteasome. Science 1999; 283: 978-81
27. Meng L, Mohan R, Kwok BH, et al. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proc Natl Acad Sci U S A 1999; 96: 10403-8
28. Koguchi Y, Kohno J, Nishio M, et al. TMC-95A, B, C, and D, novel proteasome inhibitors produced by Apiospora montagnei Sacc. TC 1093: taxonomy, production, isolation, and biological activities. J Antibiot (Tokyo) 2000; 53: 105-9
29. Kroll M, Arenzana-Seisdedos F, Bachelerie F, et al. The secondary fungal metabolite gliotoxin targets proteolytic activities of the proteasome. Chem Biol 1999; 6: 689-98
30. Nam S, Smith DM, Dou QP. Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo. J Biol Chem 2001; 276: 13322-30
31. Chung FL, Schwartz J, Herzog CR, et al. Tea and cancer prevention: studies in animals and humans. J Nutr 2003; 133 (10): 3268S-74S
32. Siddiqui IA, Afaq F, Adhami VM, et al. Antioxidants of the beverage tea in promotion of human health. Antioxid Redox Signal 2004; 6: 571-82
33. Kane RC, Bross PF, Farrell AT, et al. Velcade: US FDA approval for the treatment of multiple myeloma progressing on prior therapy. Oncologist 2003; 8: 508-13
34. An WG, Hwang SG, Trepel JB, et al. Protease inhibitor-induced apoptosis: accumulation of wt p53, p21WAF1/CIP1, and induction of apoptosis are independent markers of proteasome inhibition. Leukemia 2000; 14: 1276-83
35. Wu Y, Luo H, Kanaan N, et al. The proteasome controls the expression of a proliferation-associated nuclear antigen Ki-67. J Cell Biochem 2000; 76: 596-604
36. MacLaren AP, Chapman RS, Wyllie AH, et al. p53-dependent apoptosis induced by proteasome inhibition in mammary epithelial cells. Cell Death Differ 2001; 8: 210-8
37. Drexler HC. Activation of the cell death program by inhibition of proteasome function. Proc Natl Acad Sci U S A 1997; 94: 855-60
38. Ciechanover A, DiGiuseppe JA, Bercovich B, et al. Degradation of nuclear oncoproteins by the ubiquitin system in vitro. Proc Natl Acad Sci U S A 1991; 88: 139-43
39. Chowdary DR, Dermody JJ, Jha KK, et al. Accumulation of p53 in a mutant cell line defective in the ubiquitin pathway. Mol Cell Biol 1994; 14: 1997-2003
40. Maki CG, Huibregtse JM, Howley PM. In vivo ubiquitination and proteasome-mediated degradation of p53(1). Cancer Res 1996; 56: 2649-54
41. Dietrich C, Bartsch T, Schanz F, et al. p53-dependent cell cycle arrest induced by N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal in platelet-derived growth factor-stimulated human fibroblasts. Proc Natl Acad Sci U S A 1996; 93: 10815-9
42. Blagosklonny MV, Wu GS, Omura S, et al. Proteasome-dependent regulation of p21WAF1/CIP1 expression. Biochem Biophys Res Commun 1996; 227: 564-9
43. Shinohara K, Tomioka M, Nakano H, et al. Apoptosis induction resulting from proteasome inhibition. Biochem J 1996; 317 (Pt 2): 385-8
44. Kurland JF, Meyn RE. Protease inhibitors restore radiation-induced apoptosis to Bcl-2-expressing lymphoma cells. Int J Cancer 2001; 96: 327-33
45. Lopes UG, Erhardt P, Yao R, et al. p53-dependent induction of apoptosis by proteasome inhibitors. J Biol Chem 1997; 272: 12893-6
46. An B, Goldfarb RH, Siman R, et al. Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin dependent kinase inhibitor p27 and induce apoptosis in transformed, but not normal, human fibroblasts. Cell Death Differ 1998; 5: 1062-75
47. Naujokat C, Sezer O, Zinke H, et al. Proteasome inhibitors induced caspase dependent apoptosis and accumulation of p21WAF1/Cip1 in human immature leukemic cells. Eur J Haematol 2000; 65: 221-36
48. Herrmann JL, Beham AW, Sarkiss M, et al. Bcl-2 suppresses apoptosis resulting from disruption of the NF-kappa B survival pathway. Exp Cell Res 1997; 237: 101-9
49. Shah SA, Potter MW, McDade TP, et al. 26S proteasome inhibition induces apoptosis and limits growth of human pancreatic cancer. J Cell Biochem 2001; 82: 110-22
50. Machiels BM, Henfling ME, Gerards WL, et al. Detailed analysis of cell cycle kinetics upon proteasome inhibition. Cytometry 1997; 28: 243-52
51. Ahrendt SA, Brown HM, Komorowski RA, et al. p21WAF1 expression is associated with improved survival after adjuvant chemoradiation for pancreatic cancer. Surgery 2000; 128: 520-30
52. Loda M, Cukor B, Tam SW, et al. Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med 1997; 3: 231-4
53. Catzavelos C, Bhattacharya N, Ung YC, et al. Decreased levels of the cell-cycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer. Nat Med 1997; 3: 227-30
54. Chiarle R, Budel LM, Skolnik J, et al. Increased proteasome degradation of cyclin-dependent kinase inhibitor p27 is associated with a decreased overall survival in mantle cell lymphoma. Blood 2000; 95: 619-26
55. Chen F, Chang D, Goh M, et al. Role of p53 in cell cycle regulation and apoptosis following exposure to proteasome inhibitors. Cell Growth Differ 2000; 11: 239-46
56. Adams J, Palombella VJ, Sausville EA, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 1999; 59: 2615-22
57. Grimm LM, Goldberg AL, Poirier GG, et al. Proteasomes play an essential role in thymocyte apoptosis. EMBO J 1996; 15: 3835-44
58. Sadoul R, Fernandez PA, Quiquerez AL, et al. Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons. EMBO J 1996; 15: 3845-52
59. Li B, Dou QP. Bax degradation by the ubiquitin/proteasome-dependent pathway: involvement in tumor survival and progression. Proc Natl Acad Sci U S A 2000; 97: 3850-5
60. Yang Y, Ikezoe T, Saito T, et al. Proteasome inhibitor PS-341 induces growth arrest and apoptosis of non-small cell lung cancer cells via the JNK/c-Jun/AP-1 signaling. Cancer Sci 2004; 95: 176-80
61. Kennedy NJ, Davis RJ. Role of JNK in tumor development. Cell Cycle 2003; 2: 199-201
62. Meriin AB, Gabai VL, Yaglom J, et al. Proteasome inhibitors activate stress kinases and induce Hsp72. Diverse effects on apoptosis. J Biol Chem 1998; 273: 6373-9
63. Tsurumi C, Ishida N, Tamura T, et al. Degradation of c-Fos by the 26S proteasome is accelerated by c-Jun and multiple protein kinases. Mol Cell Biol 1995; 15: 5682-7
64. Gross-Mesilaty S, Reinstein E, Bercovich B, et al. Basal and human papillomavirus E6 oncoprotein-induced degradation of Myc proteins by the ubiquitin pathway. Proc Natl Acad Sci U S A 1998; 95: 8058-63
65. Latres E, Chiaur DS, Pagano M. The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin. Oncogene 1999; 18: 849-54
66. Angel P, Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1991; 1072: 129-57
67. Askew DS, Ashmun RA, Simmons BC, et al. Constitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis. Oncogene 1991; 6: 1915-22
68. Palombella VJ, Rando OJ, Goldberg AL, et al. The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B. Cell 1994; 78: 773-85
69. Lin YC, Brown K, Siebenlist U. Activation of NF-kappa B requires proteolysis of the inhibitor I kappa B-alpha: signal-induced phosphorylation of I kappa B-alpha alone does not release active NF-kappa B. Proc Natl Acad Sci U S A 1995; 92: 552-6
70. Roff M, Thompson J, Rodriguez MS, et al. Role of IkappaBalpha ubiquitination in signal-induced activation of NFkappaB in vivo. J Biol Chem 1996; 271: 7844-50
71. Kucharczak J, Simmons MJ, Fan Y, et al. To be, or not to be: NF-kappaB is the answer -role of Rel/NF-kappaB in the regulation of apoptosis. Oncogene 2003; 22: 8961-82
72. Karin M, Cao Y, Greten FR, et al. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2002; 2: 301-10
73. Baldwin Jr AS. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 1996; 14: 649-83
74. Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcrip-tion factor NF-kappaB. J Clin Invest 2001; 107: 241-6
75. Scherer DC, Brockman JA, Chen Z, et al. Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination. Proc Natl Acad Sci U S A 1995; 92: 11259-63
76. Chen Z, Hagler J, Palombella VJ, et al. Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway. Genes Dev 1995; 9: 1586-97
77. Winston JT, Strack P, Beer-Romero P, et al. The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. Genes Dev 1999; 13: 270-83
78. Papandreou CN, Logothetis CJ. Bortezomib as a potential treatment for prostate cancer. Cancer Res 2004; 64: 5036-43
79. Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 1999; 18: 6853-66
80. Brown K, Park S, Kanno T, et al. Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha. Proc Natl Acad Sci U S A 1993; 90: 2532-6
81. Yin L, Hubbard AK, Giardina C. NF-kappa B regulates transcription of the mouse telomerase catalytic subunit. J Biol Chem 2000; 275: 36671-5
82. Gilmore TD, Koedood M, Piffat KA, et al. Rel/NF-kappaB/IkappaB proteins and cancer. Oncogene 1996; 13: 1367-78
83. Moore BE, Bose Jr HR. Expression of the v-rel oncogene in reticuloendotheliosis virus-transformed fibroblasts. Virology 1988; 162: 377-87
84. Sylla BS, Temin HM. Activation of oncogenicity of the c-rel proto-oncogene. Mol Cell Biol 1986; 6: 4709-16
85. Wang CY, Cusack Jr JC, Liu R, et al. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-kappaB. Nat Med 1999; 5: 412-7
86. Bentires-Alj M, Hellin AC, Ameyar M, et al. Stable inhibition of nuclear factor kappaB in cancer cells does not increase sensitivity to cytotoxic drugs. Cancer Res 1999; 59: 811-5
87. Dong QG, Sclabas GM, Fujioka S, et al. The function of multiple IkappaB: NFkappaB complexes in the resistance of cancer cells to Taxol-induced apoptosis. Oncogene 2002; 21: 6510-9
88. Frankel A, Man S, Elliott P, et al. Lack of multicellular drug resistance observed in human ovarian and prostate carcinoma treated with the proteasome inhibitor PS-341. Clin Cancer Res 2000; 6: 3719-28
89. Delic J, Masdehors P, Omura S, et al. The proteasome inhibitor lactacystin induces apoptosis and sensitizes chemo- and radioresistant human chronic lymphocytic leukaemia lymphocytes to TNF-alpha-initiated apoptosis. Br J Cancer 1998; 77: 1103-7
90. Wang CY, Mayo MW, Baldwin Jr AS. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-kappaB. Science 1996; 274: 784-7
91. Jeremias I, Kupatt C, Baumann B, et al. Inhibition of nuclear factor kappaB activation attenuates apoptosis resistance in lymphoid cells. Blood 1998; 91: 4624-31
92. Bold RJ, Virudachalam S, McConkey DJ. Chemosensitization of pancreatic cancer by inhibition of the 26S proteasome. J Surg Res 2001; 100: 11-7
93. Cusack Jr JC, Liu R, Houston M, et al. Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. Cancer Res 2001; 61: 3535-40
94. Teicher BA, Ara G, Herbst R, et al. The proteasome inhibitor PS-341 in cancer therapy. Clin Cancer Res 1999; 5: 2638-45
95. Russo SM, Tepper JE, Baldwin Jr AS, et al. Enhancement of radiosensitivity by proteasome inhibition: implications for a role of NF-kappaB. Int J Radiat Oncol Biol Phys 2001; 50: 183-93
96. McConkey DJ, Williams SA, Papandreou C. Role of p53 in proteasome inhibitor-based combination chemotherapy in LNCaP cells [abstract]. Proc Am Assoc Cancer Res 2000; 42: 651
97. McConkey DJ, Williams SA, Logothetis CJ, et al. Preclinical evaluation of proteasome inhibitor-based combination chemotherapy for advanced prostate cancer. Proc Am Assoc Cancer Res 2001; 42: 229-30
98. Chandra J, Niemer I, Gilbreath J, et al. Proteasome inhibitors induce apoptosis in glucocorticoid-resistant chronic lymphocytic leukemic lymphocytes. Blood 1998; 92: 4220-9
99. Pajonk F, Pajonk K, McBride WH. Apoptosis and radiosensitization of hodgkin cells by proteasome inhibition. Int J Radiat Oncol Biol Phys 2000; 47: 1025-32
100. Yang H, Assikis V, Daliani D, et al. The proteasome inhibitor PS-341 alters the chemosensitivity of prostate cancer cells [abstract]. Proc Am Assoc Cancer Res 2003; 44: 1495
101. Pervan M, Pajonk F, Sun JR, et al. Molecular pathways that modify tumor radiation response. Am J Clin Oncol 2001; 24: 481-5
102. Sunwoo JB, Chen Z, Dong G, et al. 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 2001; 7: 1419-28
103. Nawrocki ST, Bruns CJ, Harbison MT, et al. Effects of the proteasome inhibitor PS-341 on apoptosis and angiogenesis in orthotopic human pancreatic tumor xenografts. Mol Cancer Ther 2002; 1: 1243-53
104. Hussein MA. Nontraditional cytotoxic therapies for relapsed/refractory multiple myeloma. Oncologist 2002; 7 Suppl. 1: 20-9
105. Feinman R, Koury J, Thames M, et al. Role of NF-kappaB in the rescue of multiple myeloma cells from glucocorticoid-induced apoptosis by bcl-2. Blood 1999; 93: 3044-52
106. Berenson JR, Ma HM, Vescio R. The role of nuclear factor-kappaB in the biology and treatment of multiple myeloma. Semin Oncol 2001; 28: 626-33
107. Grisham MB, Palombella VJ, Elliott PJ, et al. Inhibition of NF-kappa B activation in vitro and in vivo: role of 26S proteasome. Methods Enzymol 1999; 300: 345-63
108. Hideshima T, Chauhan D, Schlossman R, et al. The role of tumor necrosis factor alpha in the pathophysiology of human multiple myeloma: therapeutic applications. Oncogene 2001; 20: 4519-27
109. Hideshima T, Chauhan D, Richardson P, et al. NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem 2002; 277: 16639-47
110. Mitsiades N, Mitsiades CS, Richardson PG, et al. The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications. Blood 2003; 101: 2377-80
111. Davis RE, Brown KD, Siebenlist U, et al. Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 2001; 194: 1861-74
112. Pham LV, Tamayo AT, Yoshimura LC, et al. Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J Immunol 2003; 171: 88-95
113. Tan C, Waldmann TA. Proteasome inhibitor PS-341, a potential therapeutic agent for adult T-cell leukemia. Cancer Res 2002; 62: 1083-6
114. 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: 3071-6
115. 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: 14374-9
116. 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: 752-7
117. Adams J. Development of the proteasome inhibitor PS-341. Oncologist 2002; 7: 9-16
118. 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: 4996-5000
119. Lightcap ES, McCormack TA, Pien CS, et al. Proteasome inhibition measurements: clinical application. Clin Chem 2000; 46: 673-83
120. O'Quigley J, Pepe M, Fisher L. Continual reassessment method: a practical design for phase 1 clinical trials in cancer. Biometrics 1990; 46: 33-48
121. Aghajanian C, Soignet S, Dizon DS, et al. A phase I trial of the novel proteasome inhibitor PS341 in advanced solid tumor malignancies. Clin Cancer Res 2002; 8: 2505-11
122. 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: 4420-7
123. Logothetis CJ, Yang H, Daliani D, et al. Dose dependent inhibition of 20S proteasome results in serum IL-6 and PSA decline in patients (PTS) with androgen-independent prostate cancer (AI PCa) treated with the proteasome inhibitor PS-341 [abstract]. Proc Am Assoc Cancer Res 2001; 20: 186a
124. Giri D, Ozen M, Ittmann M. Interleukin-6 is an autocrine growth factor in human prostate cancer. Am J Pathol 2001; 159: 2159-65
125. Twillie DA, Eisenberger MA, Carducci MA, et al. Interleukin-6: a candidate mediator of human prostate cancer morbidity. Urology 1995; 45: 542-9
126. Borsellino N, Belldegrun A, Bonavida B. Endogenous interleukin 6 is a resistance factor for cis-diamminedichloroplatinum and etoposide-mediated cytotoxicity of human prostate carcinoma cell lines. Cancer Res 1995; 55: 4633-9
127. Papandreou CN, Daliani DD, Nix D, et al. Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J Clin Oncol 2004; 22: 2108-21
128. Raza A, Lisak LA, Tahir S, et al. Myelodysplastic syndrome patients show a variety of hematologic responses to proteasome inhibitor bortezomib (PS 341) [abstract]. Blood 2002; 100: 338b
129. Hamilton AL, Eder J, Pavlick AC, et al. PS-341: phase I study of a novel proteasome inhibitor with pharmacodynamic endpoints [abstract]. Proc Am Soc Clin Oncol 2001; 20: 85a
130. Gy GK, Thomas JP, Wilding G, et al. A phase I and pharmacologic trial of two schedules of the proteasome inhibitor, PS-341 (bortezomib, velcade), in patients with advanced cancer. Clin Cancer Res 2005; 11 (9): 3410-6
131. Iqbal S, Lenz HJ, Groshen S, et al. Phase I study of PS-341 in combination with 5-FU/LV in solid tumors [abstract]. Proc Am Soc Clin Oncol 2002; 21: 93a
132. Cortes J, Thomas D, Koller C, et al. Phase I study of bortezomib in refractory or relapsed acute leukemias. Clin Cancer Res 2004; 10: 3371-6
133. Jagannath S, Barlogie B, Berenson J, et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol 2004; 127 (2): 165-72
134. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348: 2609-17
135. Shah MH, Young D, Kindler HL, et al. Phase II study of the proteasome inhibitor bortezomib (PS-341) in patients with metastatic neuroendocrine tumors. Clin Cancer Res 2004; 10 (18 Pt 1): 6111-8
136. Thomas JP, Arzoomanian R, Alberti D, et al. A phase I and pharmacodynamic study of the proteasome inhibitor PS-341 in combination with doxorubicin [abstract]. Proc Am Soc Clin Oncol 2002; 21: 93a
137. O'Connor O, Wright J, Moskowitz CH, et al. Marked clinical activity of the novel proteasome inhibitor bortezomib in patients with relapsed follicular and mantle cell lymphoma. J Clin Oncol 2005; 23 (4): 676-84
138. Goy A, Younes A, McLaughlin P, et al. Update on a phase (ph) 2 study of bortezomib in patients (pts) with relapsed or refractory indolent or aggressive non-Hodgkin's lymphomas (NHL). J Clin Oncol 2005; 23 (4): 667-75
139. Clark JW, Ryan D, Dees C, et al. Phase I dose-escalation study of the proteasome inhibitor PS-341, plus irinotecan in patients with advanced solid tumors [abstract]. Proc Am Soc Clin Oncol 2002; 21: 93a
140. Ryan DP, Eder JP, Winkelmann J, et al. Pharmacokinetic and pharmacodynamic phase I study of PS-341 and gemcitabine in patients with advanced solid tumors [abstract]. Proc Am Soc Clin Oncol 2002; 21: 95a
141. Orlowski RZ, Voorhees PM, Garcia RA, et al. Phase I study of the proteasome inhibitor bortezomib in combination with pegylated liposomal doxorubicin in patients with refractory hematologic malignancies. Blood 2005; 102 (8): 3058-65
142. Zangari M, Barlogie B, Prather J, et al. Marked activity also in Del 13 multiple myeloma (MM) of PS 341 (PS) and subsequent thalidomide (THAL) in a setting of resistance to post-autotransplant salvage therapies [abstract]. Blood 2002; 100: 105a
143. Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation: Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplant. Br J Haematol 1998; 102: 1115-23
144. Richardson P, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dex-amethasone for relapsed muliple myeloma. N Engl J Med 2005; 352 (24): 287-98
145. Jagannath S, Durie BGM, Wolf J, et al. First-line therapy with bortezomib (VELCADE., Formerly PS-341) in patients with multiple myeloma (MM) [abstract]. J Clin Oncol 2004; 22 Suppl 14s: 570s
146. Cavenagh J, Curry N, Stec J, et al. PAD Therapy (Bortezomib, Adriamycin and dexamethasone) for untreated Multiple Myeloma (MM) [abstract]. J Clin Oncol 2004; 22 Suppl 14s: 570s
147. Yang HH, Vescio R, Schenkein D, et al. A prospective, open-label safety and efficacy study of combination treatment with bortezomib (PS-341, velcade and melphalan in patients with relapsed or refractory multiple myeloma. Clin Lymphoma 2003; 4: 119-22
148. Zangari M, Barlogie B, Jacobson J, et al. VTD regimen comprising Velcade (V) + Thalidomide (T) and added DEX (D) for non-responders to V + T effects a 57% PR rate among 56 patients with myeloma (M) relapsing after autologous transplant [abstract]. Blood 2003; 102: 236a
149. Jagannath S, Richardson P, Barlogie B, et al. Phase II trials of bortezomib in combination with dexamethasone in multiple myeloma (MM): assessment of additional benefits to combination in patients with sub-optimal responses to bortezomib alone [abstract no. 2341]. Proc Am Soc Clin Oncol 2003; 22: 582
150. Shaughnessy J, Zhan F, McCastlain K, et al. Gene expression profiling in the prediction of response of multiple myeloma to the proteasome inhibitor PS-341 [abstract]. Blood 2002; 100: 390a
151. Shaughnessy J, Zhan F, Kordsmeier B, et al. Gene expression profiling (GEP) after short term in-vivo treatment identifies potential mechanisms of action of current drugs used to treat multiple myeloma [abstract]. Blood 2002; 100: 208a
152. Richardson PG, Barlogie B, Berenson J, et al. Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myelo-ma. Blood. Epub 2005 Jul 14