Preclinical activity of the oral proteasome inhibitor mln9708 in myeloma bone disease

Clinical Cancer Research

Volumn 20, Issue 6, 2014, Pages 1542-1554

  Garcia Gomez, Antonio ^a,b,c   Quwaider, Dalia ^a   Canavese, Miriam ^e   Ocio, Enrique M ^a,c   Tian, Ze ^f   Blanco, Juan F ^c   Berger, Allison J ^g   Ortiz de Solorzano, Carlos ^d   Hernandez Iglesias, Teresa ^a   Martens, Anton C M ^h   Groen, Richard W J ^h   Mateo Urdiales, Joaqún ^d   Fraile, Susana ^a   Galarraga, Miguel ^d   Chauhan, Dharminder ^f   Miguel, Jesus F San ^a,b,c   Raje, Noopur ^e   Garayoa, Mercedes ^a,b,c  

^a CSIC   (Spain)

^b ISCIII)   (Spain)

^c HOSPITAL UNIVERSITARIO DE SALAMANCA   (Spain)

^d UNIVERSITY OF NAVARRA   (Spain)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

^f HARVARD MEDICAL SCHOOL   (United States)

^g MILLENNIUM PHARMACEUTICALS INC   (United States)

^h UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CATENIN; BORTEZOMIB; F ACTIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IXAZOMIB; MELPHALAN; OSTEOCLAST DIFFERENTIATION FACTOR; PROTEIN IRE1; T LYMPHOCYTE RECEPTOR; VITRONECTIN RECEPTOR; ANTINEOPLASTIC AGENT; BORON DERIVATIVE; GLYCINE; IXAZOMIB CITRATE; PROTEASOME INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; BONE ATROPHY; BONE CANCER; BONE MINERALIZATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG MECHANISM; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MITOSIS INHIBITION; MOUSE; MULTIPLE MYELOMA; NONHUMAN; OSTEOBLAST; OSTEOCLASTOGENESIS; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; ANALOGS AND DERIVATIVES; ANIMAL; CELL LINE; DISEASE MODEL; DRUG EFFECTS; IMMUNOBLOTTING; MESENCHYMAL STROMA CELL; METABOLISM; NONOBESE DIABETIC MOUSE; OSTEOCLAST; OSTEOLYSIS; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCID MOUSE;

ANIMALS; ANTINEOPLASTIC AGENTS; BONE RESORPTION; BORON COMPOUNDS; CELL LINE; DISEASE MODELS, ANIMAL; GLYCINE; HUMANS; IMMUNOBLOTTING; MESENCHYMAL STROMAL CELLS; MICE; MICE, INBRED NOD; MICE, SCID; MULTIPLE MYELOMA; OSTEOCLASTS; PROTEASOME INHIBITORS; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION;

EID: 84896511237     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-13-1657     Document Type: Article

References (49)

1. Kyle RA, Rajkumar SV. Multiple myeloma. Blood 2008;111:2962-72.
2. Raje N, Roodman GD. Advances in the biology and treatment of bone disease in multiple myeloma. Clin Cancer Res 2011;17:1278-86.
3. Vallet S, Raje N. Bone anabolic agents for the treatment of multiple myeloma. Cancer Microenviron 2011;4:339-49.
4. Basak GW, Srivastava AS, Malhotra R, Carrier E. Multiple myeloma bone marrow niche. Curr Pharm Biotechnol 2009;10:345-6.
5. Yaccoby S. Advances in the understanding of myeloma bone disease and tumour growth. Br J Haematol 2010;149:311-21.
6. Giuliani N, Colla S, Morandi F, Lazzaretti M, Sala R, Bonomini S, et al. Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood 2005;106:2472-83.
7. Ocio EM, Mateos MV, San-Miguel JF. Novel agents derived from the currently approved treatments for MM: novel proteasome inhibitors and novel IMIDs. Expert Opin Investig Drugs 2012;21:1075-87.
8. Dick LR, Fleming PE. Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Discov Today 2010;15:243-9.
9. Hideshima T, Anderson KC. Preclinical studies of novel targeted therapies. Hematol Oncol Clin North Am 2007;21:1071-91.
10. Terpos E, Dimopoulos MA, Sezer O, Roodman D, Abildgaard N, Vescio R, et al. The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group. Leukemia 2010;24:1700-12.
11. Delforge M, Terpos E, Richardson PG, Shpilberg O, Khuageva NK, Schlag R, et al. Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma. Eur J Haematol 2011;86: 372-84.
12. Zangari M, Yaccoby S, Pappas L, Cavallo F, Kumar NS, Ranganathan S, et al. A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients. Haematologica 2011;96: 333-6.
13. von Metzler I, Krebbel H, Hecht M, Manz RA, Fleissner C, Mieth M, et al. Bortezomib inhibits human osteoclastogenesis. Leukemia 2007;21: 2025-34.
14. Oyajobi BO, Garrett IR, Gupta A, Flores A, Esparza J, Munoz S, et al. Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease. Br J Haematol 2007;139:434-8.
15. Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Bonomini S, Crugnola M, et al. The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients. Blood 2007;110:334-8.
16. Mukherjee S, Raje N, Schoonmaker JA, Liu JC, Hideshima T, Wein MN, et al. Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. J Clin Invest 2008;118:491-504.
17. Pennisi A, Li X, Ling W, Khan S, Zangari M, Yaccoby S. The proteasome inhibitor, bortezomib suppresses primary myeloma and stimulates bone formation in myelomatous and nonmyelomatous bones in vivo. Am J Hematol 2009;84:6-14.
18. Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res 2010;70:1970-80.
19. Chauhan D, Tian Z, Zhou B, Kuhn D, Orlowski R, Raje N, et al. In vitro and in vivo selective antitumor activity of a novel orally bioavailable proteasome inhibitor MLN9708 against multiple myeloma cells. Clin Cancer Res 2011;17:5311-21.
20. Kumar S, Bensinger WI, Reeder CB, Zimmerman TM, Berenson JR, Berg D, et al. Weekly dosing of the investigational oral proteasome inhibitor MLN9708 in patients with relapsed and/or refractory multiple myeloma: results from a phase 1 dose-escalation study. Blood (ASH Annual Meeting Abstracts) 2011;118:371-2. Abstract 816.
21. Richardson PG, Baz R, Wang L, Jakubowiak AJ, Berg D, Liu G, et al. Investigational agent MLN9708, an oral proteasome inhibitor, in patients (Pts) with relapsed and/or refractory multiple myeloma (MM): results from the expansion cohorts of a phase 1 dose-escalation study. Blood (ASH Annual Meeting Abstracts) 2011;118:140. Abstract 301.
22. Kumar SK, Berdeja JG, Niesvizky R, Lonial S, Hamadani M, Stewart AK, et al. A phase 1/2 study of weeklyMLN9708, an investigational oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma (MM). Blood (ASH Annual Meeting Abstracts) 2012;120. Abstract 332.
23. Lee EC, Fitzgerald M, Bannerman B, Donelan J, Bano K, Terkelsen J, et al. Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse models of B-cell and plasma cell malignancies. Clin Cancer Res 2011;17:7313-23.
24. Groen RW, Noort WA, Raymakers RA, Prins HJ, Aalders L, Hofhuis FM, et al. Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma. Blood 2012;120:e9-16.
25. Garayoa M, Garcia JL, Santamaria C, Garcia-Gomez A, Blanco JF, Pandiella A, et al. Mesenchymal stem cells from multiple myeloma patients display distinct genomic profile as compared with those from normal donors. Leukemia 2009;23:1515-27.
26. Garcia-Gomez A, Ocio EM, Crusoe E, Santamaria C, Hernandez-Campo P, Blanco JF, et al. Dasatinib as a bone-modifying agent: anabolic and anti-resorptive effects. PLoS ONE 2012;7:e34914.
27. Hurchla MA, Garcia-Gomez A, Hornick MC, Ocio EM, Li A, Blanco JF, et al. The epoxyketone-based proteasome inhibitors carfilzomib and orally bioavailable oprozomib have anti-resorptive and bone-Anabolic activity in addition to anti-myeloma effects. Leukemia 2013;27: 430-40.
28. Veeman MT, Slusarski DC, Kaykas A, Louie SH, Moon RT. Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements. Curr Biol 2003;13:680-5.
29. Doube M, Klosowski MM, Arganda-Carreras I, Cordelieres FP, Dougherty RP, Jackson JS, et al. BoneJ: free and extensible bone image analysis in ImageJ. Bone 2010;47:1076-9.
30. Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC. Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev 2007;7:585-98.
31. Breitkreutz I, Raab MS, Vallet S, Hideshima T, Raje N, Mitsiades C, et al. Lenalidomide inhibits osteoclastogenesis, survival factors, and boneremodeling markers in multiple myeloma. Leukemia 2008;22:1925-32.
32. Kuroda Y, Matsuo K. Molecular mechanisms of triggering, amplifying, and targeting RANK signaling in osteoclasts. World J Orthop 2012;3: 167-74.
33. Ang E, Pavlos NJ, Rea SL, Qi M, Chai T, Walsh JP, et al. Proteasome inhibitors impair RANKL-induced NF-kappaBactivity in osteoclast-like cells via disruption of p62, TRAF6, CYLD, and IkappaBalpha signaling cascades. J Cell Physiol 2009;220:450-9.
34. Vaananen HK, Laitala-Leinonen T. Osteoclast lineage and function. Arch Biochem Biophys 2008;473:132-8.
35. Lin GL, Hankenson KD. Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J Cell Biochem 2011;112: 3491-501.
36. Monroe DG, McGee-Lawrence ME, Oursler MJ, Westendorf JJ. Update on Wnt signaling in bone cell biology and bone disease. Gene 2012;492:1-18.
37. Qiang YW, Hu B, Chen Y, Zhong Y, Shi B, Barlogie B, et al. Bortezomib induces osteoblast differentiation via Wnt-independent activation of beta-catenin/TCF signaling. Blood 2009;113:4319-30.
38. Sutherland C, Leighton IA, Cohen P. Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase connections in insulin and growth-factor signalling. Biochem J 1993;296:15-9.
39. Tohmonda T, Miyauchi Y, Ghosh R, Yoda M, Uchikawa S, Takito J, et al. The IRE1alpha-XBP1 pathway is essential for osteoblast differentiation through promoting transcription of Osterix. EMBO Rep 2011;12:451-7.
40. Longo V, Brunetti O, D'Oronzo S, Dammacco F, Silvestris F. Therapeutic approaches to myeloma bone disease: an evolving story. Cancer Treat Rev 2012;38:787-97.
41. Sonmez M, Akagun T, Topbas M, Cobanoglu U, Sonmez B, Yilmaz M, et al. Effect of pathologic fractures on survival in multiple myeloma patients: a case control study. J Exp Clin Cancer Res 2008;27:11.
42. Wu P, Morgan GJ. Targeting bone as a therapy for myeloma. Cancer Microenviron 2011;4:299-311.
43. Drake MT, Clarke BL, Khosla S. Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clin Proc 2008;83:1032-45.
44. Terpos E, Sezer O, Croucher PI, Garcia-Sanz R, Boccadoro M, San Miguel J, et al. The use of bisphosphonates in multiple myeloma: recommendations of an expert panel on behalf of the European Myeloma Network. Ann Oncol 2009;20:1303-17.
45. Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood 2007;110:3281-90.
46. Chauhan D, Singh AV, Aujay M, Kirk CJ, Bandi M, Ciccarelli B, et al. A novel orally active proteasome inhibitor ONX 0912 triggers in vitro and in vivo cytotoxicity in multiple myeloma. Blood 2011;116: 4906-15.
47. Hu B, Chen Y, Usmani SZ, Ye S, Qiang W, Papanikolaou X, et al. Characterization of the molecular mechanism of the bone-Anabolic activity of carfilzomib in multiple myeloma. PLoS ONE 2013;8: e74191.
48. Obeng EA, Carlson LM, Gutman DM, Harrington WJ Jr., Lee KP, Boise LH. Proteasomeinhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood 2006;107:4907-16.
49. Gupta N, Noe D, Liu G, Berg D, Kalebic T, Shou Y, et al. Clinical pharmacokinetics of intravenous and oralMLN9708, an investigational proteasome inhibitor: pooled analysis from monotherapy and combinations studies across various indications. Clin Pharmacol Ther (ASCPT Annual Meeting Abstracts) 2013;93:S32. Abstract PI-51.