nach oben

Cancer Microenvironment

Erschienen in:

01.12.2011 | Original Paper

Bone Anabolic Agents for the Treatment of Multiple Myeloma

verfasst von: Sonia Vallet, Noopur Raje

Erschienen in: Cancer Microenvironment | Ausgabe 3/2011

Einloggen, um Zugang zu erhalten

Abstract

The majority of patients with multiple myeloma develop bone osteolytic lesions, which may lead to severe complications, including pain and fractures. The pathogenesis of bone disease depends on uncoupled bone remodeling, characterized by increased bone resorption due to upregulation of osteoclast activity and decreased bone formation due to osteoblast inhibition. In myeloma, impaired osteoblast differentiation and increased apoptosis have been described. Responsible for these effects are integrin-mediated adhesion to tumor cells and soluble factors, including WNT antagonists, BMP2 inhibitors and numerous cytokines. Based on the evidence of osteoblast suppression in myeloma, bone anabolic agents have been developed and are currently undergoing clinical evaluation. Due to bidirectional inhibitory effects characterizing tumor cells and osteoblasts interactions, agents targeting osteoblasts are expected to reduce tumor burden along with improvement of bone health. This review summarizes the current knowledge on osteoblast inhibition in myeloma and provides an overview on the clinical grade agents with bone anabolic properties, which represent new promising therapeutic strategies in myeloma.

Roodman GD (2006) New potential targets for treating myeloma bone disease. Clin Cancer Res 12(20 Pt 2):6270s–6273sPubMedCrossRef

Coleman RE (1997) Skeletal complications of malignancy. Cancer 80(8 Suppl):1588–1594PubMedCrossRef

Saad F, Lipton A, Cook R, Chen YM, Smith M, Coleman R (2007) Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 110(8):1860–1867PubMedCrossRef

Valentin-Opran A, Charhon SA, Meunier PJ, Edouard CM, Arlot ME (1982) Quantitative histology of myeloma-induced bone changes. Br J Haematol 52(4):601–610PubMedCrossRef

Bataille R, Chappard D, Marcelli C, Dessauw P, Sany J, Baldet P, Alexandre C (1989) Mechanisms of bone destruction in multiple myeloma: the importance of an unbalanced process in determining the severity of lytic bone disease. J Clin Oncol 7(12):1909–1914PubMed

Taube T, Beneton MN, McCloskey EV, Rogers S, Greaves M, Kanis JA (1992) Abnormal bone remodelling in patients with myelomatosis and normal biochemical indices of bone resorption. Eur J Haematol 49(4):192–198PubMedCrossRef

Lentzsch S, Gries M, Janz M, Bargou R, Dorken B, Mapara MY (2003) Macrophage inflammatory protein 1-alpha (MIP-1 alpha) triggers migration and signaling cascades mediating survival and proliferation in multiple myeloma (MM) cells. Blood 101(9):3568–3573PubMedCrossRef

Podar K, Anderson KC (2005) The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications. Blood 105(4):1383–1395PubMedCrossRef

Alsayed Y, Ngo H, Runnels J, Leleu X, Singha UK, Pitsillides CM, Spencer JA, Kimlinger T, Ghobrial JM, Jia X, Lu G, Timm M, Kumar A, Cote D, Veilleux I, Hedin KE, Roodman GD, Witzig TE, Kung AL, Hideshima T, Anderson KC, Lin CP, Ghobrial IM (2007) Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma. Blood 109(7):2708–2717PubMed

10.

Yaccoby S, Wezeman MJ, Zangari M, Walker R, Cottler-Fox M, Gaddy D, Ling W, Saha R, Barlogie B, Tricot G, Epstein J (2006) Inhibitory effects of osteoblasts and increased bone formation on myeloma in novel culture systems and a myelomatous mouse model. Haematologica 91(2):192–199PubMed

11.

Giuliani N, Rizzoli V, Roodman GD (2006) Multiple myeloma bone disease: pathophysiology of osteoblast inhibition. Blood 108(13):3992–3996PubMedCrossRef

12.

Jemal A, Siegel R, Xu J, Ward E Cancer statistics, 2010. CA: a cancer journal for clinicians 60 (5):277–300

13.

Franz-Odendaal TA, Hall BK, Witten PE (2006) Buried alive: how osteoblasts become osteocytes. Dev Dyn 235(1):176–190PubMedCrossRef

14.

Komori T (2006) Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 99(5):1233–1239PubMedCrossRef

15.

Edwards CM, Edwards JR, Lwin ST, Esparza J, Oyajobi BO, McCluskey B, Munoz S, Grubbs B, Mundy GR (2008) Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo. Blood 111(5):2833–2842PubMedCrossRef

16.

Li X, Pennisi A, Yaccoby S (2008) Role of decorin in the antimyeloma effects of osteoblasts. Blood 112(1):159–168PubMedCrossRef

17.

Giuliani N, Bataille R, Mancini C, Lazzaretti M, Barille S (2001) Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment. Blood 98(13):3527–3533PubMedCrossRef

18.

Qiang YW, Chen Y, Stephens O, Brown N, Chen B, Epstein J, Barlogie B, Shaughnessy JD Jr (2008) Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma. Blood 112(1):196–207PubMedCrossRef

19.

Sims NA, Gooi JH (2008) Bone remodeling: multiple cellular interactions required for coupling of bone formation and resorption. Semin Cell Dev Biol 19(5):444–451PubMedCrossRef

20.

Silvestris F, Cafforio P, Calvani N, Dammacco F (2004) Impaired osteoblastogenesis in myeloma bone disease: role of upregulated apoptosis by cytokines and malignant plasma cells. Br J Haematol 126(4):475–486PubMedCrossRef

21.

Giuliani N, Storti P, Abeltino M, Bolzoni M, Ferretti M, Lazzaretti M, Dalla Palma B, Todoerti K, Martella E, Agnelli L, Neri A, Rizzoli V, Palumbo C (2010) In vitro and in vivo evidences of osteocyte involvement in myeloma-induced osteolysis. Blood:Abstract 131

22.

Giuliani N, Colla S, Morandi F, Lazzaretti M, Sala R, Bonomini S, Grano M, Colucci S, Svaldi M, Rizzoli V (2005) Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood 106(7):2472–2483PubMedCrossRef

23.

Komori T Regulation of bone development and extracellular matrix protein genes by RUNX2. Cell and tissue research 339(1):189–195

24.

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89(5):755–764PubMedCrossRef

25.

Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, de Crombrugghe B (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108(1):17–29PubMedCrossRef

26.

Baek WY, de Crombrugghe B, Kim JE Postnatally induced inactivation of Osterix in osteoblasts results in the reduction of bone formation and maintenance. Bone 46 (4):920–928

27.

Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2005) Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem 280(39):33132–33140PubMedCrossRef

28.

Takada I, Mihara M, Suzawa M, Ohtake F, Kobayashi S, Igarashi M, Youn MY, Takeyama K, Nakamura T, Mezaki Y, Takezawa S, Yogiashi Y, Kitagawa H, Yamada G, Takada S, Minami Y, Shibuya H, Matsumoto K, Kato S (2007) A histone lysine methyltransferase activated by non-canonical Wnt signalling suppresses PPAR-gamma transactivation. Nat Cell Biol 9(11):1273–1285PubMedCrossRef

29.

Giuliani N, Mangoni M, Rizzoli V (2009) Osteogenic differentiation of mesenchymal stem cells in multiple myeloma: identification of potential therapeutic targets. Exp Hematol 37(8):879–886PubMedCrossRef

30.

Tian E, Zhan F, Walker R, Rasmussen E, Ma Y, Barlogie B, Shaughnessy JD Jr (2003) The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 349(26):2483–2494PubMedCrossRef

31.

Yaccoby S, Ling W, Zhan F, Walker R, Barlogie B, Shaughnessy JD Jr (2007) Antibody-based inhibition of DKK1 suppresses tumor-induced bone resorption and multiple myeloma growth in vivo. Blood 109(5):2106–2111PubMedCrossRef

32.

Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Donofrio G, Bonomini S, Sala R, Mangoni M, Rizzoli V (2007) Production of Wnt inhibitors by myeloma cells: potential effects on canonical Wnt pathway in the bone microenvironment. Cancer Res 67(16):7665–7674PubMedCrossRef

33.

Fulciniti M, Tassone P, Hideshima T, Vallet S, Nanjappa P, Ettenberg SA, Shen Z, Patel N, Tai YT, Chauhan D, Mitsiades C, Prabhala R, Raje N, Anderson KC, Stover DR, Munshi NC (2009) Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma. Blood 114(2):371–379PubMedCrossRef

34.

Heath DJ, Chantry AD, Buckle CH, Coulton L, Shaughnessy JD, Evans HR, Snowden JA, Stover DR, Vanderkerken K, Croucher PI (2009) Inhibiting Dickkopf-1 (Dkk1) removes suppression of bone formation and prevents the development of osteolytic bone disease in multiple myeloma. J Bone Miner Res 24(3):425–436

35.

Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, Foernzler D, Van Hul W (2001) Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet 10(5):537–543PubMedCrossRef

36.

Winkler DG, Sutherland MK, Geoghegan JC, Yu C, Hayes T, Skonier JE, Shpektor D, Jonas M, Kovacevich BR, Staehling-Hampton K, Appleby M, Brunkow ME, Latham JA (2003) Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J 22(23):6267–6276PubMedCrossRef

37.

Terpos E, Christoulas D, Katodritou E, Bratengeier C, Lindner C, Harmelin S, Hawa G, Boutsikas G, Migkou M, Gavriatopoulou M, Michalis E, Pouli C, Kastritis E, K Z, Dimopoulos MA (2009) High serum sclerostin correlates with advanced stage, increased bone resorption, reduced osteoblast function, and poor survival in newly-diagnosed patients with multiple myeloma Blood: Abstract 425

38.

Colucci S, Brunetti G, Oranger A, Mori G, Sardone F, Liso V, Curci P, Miccolis R, Rinaldi E, Specchia G, Passeri G, Zallone A, Rizzi R, Grano M (2010) Myeloma cells induce osteoblast suppression through sclerostin secretion. Blood:Abstract 2961

39.

Oshima T, Abe M, Asano J, Hara T, Kitazoe K, Sekimoto E, Tanaka Y, Shibata H, Hashimoto T, Ozaki S, Kido S, Inoue D, Matsumoto T (2005) Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood 106(9):3160–3165PubMedCrossRef

40.

Ryoo HM, Lee MH, Kim YJ (2006) Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene 366(1):51–57PubMedCrossRef

41.

Woodruff TK (1998) Regulation of cellular and system function by activin. Biochem Pharmacol 55(7):953–963PubMedCrossRef

42.

Derynck R, Akhurst RJ, Balmain A (2001) TGF-beta signaling in tumor suppression and cancer progression. Nat Genet 29(2):117–129PubMedCrossRef

43.

Samee N, Geoffroy V, Marty C, Schiltz C, Vieux-Rochas M, Levi G, de Vernejoul MC (2008) Dlx5, a positive regulator of osteoblastogenesis, is essential for osteoblast-osteoclast coupling. Am J Pathol 173(3):773–780PubMedCrossRef

44.

Holleville N, Quilhac A, Bontoux M, Monsoro-Burq AH (2003) BMP signals regulate Dlx5 during early avian skull development. Dev Biol 257(1):177–189PubMedCrossRef

45.

Bennett CN, Longo KA, Wright WS, Suva LJ, Lane TF, Hankenson KD, MacDougald OA (2005) Regulation of osteoblastogenesis and bone mass by Wnt10b. Proc Natl Acad Sci U S A 102(9):3324–3329PubMedCrossRef

46.

Lee MH, Kim YJ, Kim HJ, Park HD, Kang AR, Kyung HM, Sung JH, Wozney JM, Kim HJ, Ryoo HM (2003) BMP-2-induced Runx2 expression is mediated by Dlx5, and TGF-beta 1 opposes the BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression. J Biol Chem 278(36):34387–34394PubMedCrossRef

47.

Vallet S, Mukherjee S, Vaghela N, Hideshima T, Fulciniti M, Pozzi S, Santo L, Cirstea D, Patel K, Sohani R, Guimaraes A, Xie W, Chauhan D, Schoonmaker J, Attar E, Churchill M, Weller E, Munshi N, Seehra J, Weissleder R, Anderson K, Scadden D, Raje N (2010) Activin A promotes multiple myeloma-induced osteolysis and is a promising target for myeloma bone disease. Proc Natl Acad Sci U S A 107(11):5124–5129

48.

Terpos E, Christoulas D, Kastritis E, Gkotzamanidou M, Gavriatopoulou M, Eleutherakis-Papaiakovou E, Migkou M, Roussou M, Papatheodorou A, Dimopoulos MA (2010) Elevated levels of circulating activin-A correlate with features of advanced disease, extensive bone involvement and inferior survival in patients with multiple myeloma. Blood:Abstract 2967

49.

Fuller K, Bayley KE, Chambers TJ (2000) Activin A is an essential cofactor for osteoclast induction. Biochem Biophys Res Commun 268(1):2–7PubMedCrossRef

50.

Shiozaki M, Sakai R, Tabuchi M, Nakamura T, Sugino K, Sugino H, Eto Y (1992) Evidence for the participation of endogenous activin A/erythroid differentiation factor in the regulation of erythropoiesis. Proc Natl Acad Sci U S A 89(5):1553–1556PubMedCrossRef

51.

Matzuk MM, Kumar TR, Bradley A (1995) Different phenotypes for mice deficient in either activins or activin receptor type II. Nature 374(6520):356–360PubMedCrossRef

52.

Chantry AD, Heath D, Mulivor AW, Pearsall S, Baud’huin M, Coulton L, Evans H, Abdul N, Werner ED, Bouxsein ML, Key ML, Seehra J, Arnett TR, Vanderkerken K, Croucher P (2010) Inhibiting activin-A signaling stimulates bone formation and prevents cancer induced bone destruction in vivo. J Bone Miner Res 25(12):2633–2646

53.

Alliston T, Choy L, Ducy P, Karsenty G, Derynck R (2001) TGF-beta-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO J 20(9):2254–2272PubMedCrossRef

54.

Takeuchi K, Abe M, Hiasa M, Oda A, Amou H, Kido S, Harada T, Tanaka O, Miki H, Nakamura S, Nakano A, Kagawa K, Yata K, Ozaki S, Matsumoto T Tgf-Beta inhibition restores terminal osteoblast differentiation to suppress myeloma growth. PloS one 5 (3):e9870

55.

Mohammad KS, Chen CG, Balooch G, Stebbins E, McKenna CR, Davis H, Niewolna M, Peng XH, Nguyen DH, Ionova-Martin SS, Bracey JW, Hogue WR, Wong DH, Ritchie RO, Suva LJ, Derynck R, Guise TA, Alliston T (2009) Pharmacologic inhibition of the TGF-beta type I receptor kinase has anabolic and anti-catabolic effects on bone. PloS one 4(4):e5275PubMedCrossRef

56.

Standal T, Abildgaard N, Fagerli UM, Stordal B, Hjertner O, Borset M, Sundan A (2007) HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma. Blood 109(7):3024–3030PubMed

57.

Uneda S, Hata H, Matsuno F, Harada N, Mitsuya Y, Kawano F, Mitsuya H (2003) Macrophage inflammatory protein-1 alpha is produced by human multiple myeloma (MM) cells and its expression correlates with bone lesions in patients with MM. Br J Haematol 120(1):53–55PubMedCrossRef

58.

Terpos E, Politou M, Szydlo R, Goldman JM, Apperley JF, Rahemtulla A (2003) Serum levels of macrophage inflammatory protein-1 alpha (MIP-1alpha) correlate with the extent of bone disease and survival in patients with multiple myeloma. Br J Haematol 123(1):106–109PubMedCrossRef

59.

Roussou M, Tasidou A, Dimopoulos MA, Kastritis E, Migkou M, Christoulas D, Gavriatopoulou M, Zagouri F, Matsouka C, Anagnostou D, Terpos E (2009) Increased expression of macrophage inflammatory protein-1alpha on trephine biopsies correlates with extensive bone disease, increased angiogenesis and advanced stage in newly diagnosed patients with multiple myeloma. Leukemia 23(11):2177–2181PubMedCrossRef

60.

Han JH, Choi SJ, Kurihara N, Koide M, Oba Y, Roodman GD (2001) Macrophage inflammatory protein-1alpha is an osteoclastogenic factor in myeloma that is independent of receptor activator of nuclear factor kappaB ligand. Blood 97(11):3349–3353PubMedCrossRef

61.

Tsubaki M, Kato C, Manno M, Ogaki M, Satou T, Itoh T, Kusunoki T, Tanimori Y, Fujiwara K, Matsuoka H, Nishida S (2007) Macrophage inflammatory protein-1alpha (MIP-1alpha) enhances a receptor activator of nuclear factor kappaB ligand (RANKL) expression in mouse bone marrow stromal cells and osteoblasts through MAPK and PI3K/Akt pathways. Mol Cell Biochem 304(1–2):53–60PubMedCrossRef

62.

Vallet S, Raje N, Ishitsuka K, Hideshima T, Podar K, Chhetri S, Pozzi S, Breitkreutz I, Kiziltepe T, Yasui H, Ocio EM, Shiraishi N, Jin J, Okawa Y, Ikeda H, Mukherjee S, Vaghela N, Cirstea D, Ladetto M, Boccadoro M, Anderson KC (2007) MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts. Blood 110(10):3744–3752PubMedCrossRef

63.

Menu E, De Leenheer E, De Raeve H, Coulton L, Imanishi T, Miyashita K, Van Valckenborgh E, Van Riet I, Van Camp B, Horuk R, Croucher P, Vanderkerken K (2006) Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: a study in the 5TMM model. Clin Exp Metastasis 23(5–6):291–300PubMedCrossRef

64.

Vallet S, Pozzi S, Patel K, Vaghela N, Fulciniti M, Veiby P, Hideshima T, Santo L, Cirstea D, Scadden D, Anderson K, Raje N (2011) A novel role for CCL3 (MIP-1α) in Myeloma-induced bone disease via osteocalcin downregulation and inhibition of osteoblast function. Leukemia 25(7):1174–1181

65.

Nanes MS (2003) Tumor necrosis factor-alpha: molecular and cellular mechanisms in skeletal pathology. Gene 321:1–15PubMedCrossRef

66.

Vincent C, Findlay DM, Welldon KJ, Wijenayaka AR, Zheng TS, Haynes DR, Fazzalari NL, Evdokiou A, Atkins GJ (2009) Pro-inflammatory cytokines TNF-related weak inducer of apoptosis (TWEAK) and TNFalpha induce the mitogen-activated protein kinase (MAPK)-dependent expression of sclerostin in human osteoblasts. J Bone Miner Res 24(8):1434–1449PubMedCrossRef

67.

D’Souza S, Del Prete D, Esteve F, Sammut B, Yu S, Xiao G, Galson D, Roodman D (2009) Multiple myeloma cell induction of GFI-1 in stromal cells suppresses osteoblast differentiation in patients with myeloma. Blood 114:742CrossRef

68.

Olfa G, Christophe C, Philippe L, Romain S, Khaled H, Pierre H, Odile B, Jean-Christophe D RUNX2 regulates the effects of TNFalpha on proliferation and apoptosis in SaOs-2 cells. Bone 46(4):901–910

69.

Jourdan M, Tarte K, Legouffe E, Brochier J, Rossi JF, Klein B (1999) Tumor necrosis factor is a survival and proliferation factor for human myeloma cells. Eur Cytokine Netw 10(1):65–70PubMed

70.

Lee JW, Chung HY, Ehrlich LA, Jelinek DF, Callander NS, Roodman GD, Choi SJ (2004) IL-3 expression by myeloma cells increases both osteoclast formation and growth of myeloma cells. Blood 103(6):2308–2315PubMedCrossRef

71.

Ehrlich LA, Chung HY, Ghobrial I, Choi SJ, Morandi F, Colla S, Rizzoli V, Roodman GD, Giuliani N (2005) IL-3 is a potential inhibitor of osteoblast differentiation in multiple myeloma. Blood 106(4):1407–1414PubMedCrossRef

72.

Giuliani N, Morandi F, Tagliaferri S, Colla S, Bonomini S, Sammarelli G, Rizzoli V (2006) Interleukin-3 (IL-3) is overexpressed by T lymphocytes in multiple myeloma patients. Blood 107(2):841–842PubMedCrossRef

73.

Giuliani N, Colla S, Sala R, Moroni M, Lazzaretti M, La Monica S, Bonomini S, Hojden M, Sammarelli G, Barille S, Bataille R, Rizzoli V (2002) Human myeloma cells stimulate the receptor activator of nuclear factor-kappa B ligand (RANKL) in T lymphocytes: a potential role in multiple myeloma bone disease. Blood 100(13):4615–4621PubMedCrossRef

74.

Cocco C, Giuliani N, Di Carlo E, Ognio E, Storti P, Abeltino M, Sorrentino C, Ponzoni M, Ribatti D, Airoldi I Interleukin-27 acts as multifunctional antitumor agent in multiple myeloma. Clin Cancer Res 16(16):4188–4197

75.

Zhao C, Irie N, Takada Y, Shimoda K, Miyamoto T, Nishiwaki T, Suda T, Matsuo K (2006) Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab 4(2):111–121PubMedCrossRef

76.

Pennisi A, Ling W, Li X, Khan S, Shaughnessy JD Jr, Barlogie B, Yaccoby S (2009) The ephrinB2/EphB4 axis is dysregulated in osteoprogenitors from myeloma patients and its activation affects myeloma bone disease and tumor growth. Blood 114(9):1803–1812PubMedCrossRef

77.

Berenson JR, Lichtenstein A, Porter L, Dimopoulos MA, Bordoni R, George S, Lipton A, Keller A, Ballester O, Kovacs MJ, Blacklock HA, Bell R, Simeone J, Reitsma DJ, Heffernan M, Seaman J, Knight RD (1996) Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. Myeloma Aredia Study Group. N Engl J Med 334(8):488–493PubMedCrossRef

78.

Hideshima T, Mitsiades C, Tonon G, Richardson PG, Anderson KC (2007) Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer 7(8):585–598PubMedCrossRef

79.

von Metzler I, Krebbel H, Hecht M, Manz RA, Fleissner C, Mieth M, Kaiser M, Jakob C, Sterz J, Kleeberg L, Heider U, Sezer O (2007) Bortezomib inhibits human osteoclastogenesis. Leukemia 21(9):2025–2034CrossRef

80.

Oyajobi BO, Garrett IR, Gupta A, Flores A, Esparza J, Munoz S, Zhao M, Mundy GR (2007) Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease. Br J Haematol 139(3):434–438PubMedCrossRef

81.

Giuliani N, Morandi F, Tagliaferri S, Lazzaretti M, Bonomini S, Crugnola M, Mancini C, Martella E, Ferrari L, Tabilio A, Rizzoli V (2007) The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients. Blood 110(1):334–338PubMedCrossRef

82.

Mukherjee S, Raje N, Schoonmaker JA, Liu JC, Hideshima T, Wein MN, Jones DC, Vallet S, Bouxsein ML, Pozzi S, Chhetri S, Seo YD, Aronson JP, Patel C, Fulciniti M, Purton LE, Glimcher LH, Lian JB, Stein G, Anderson KC, Scadden DT (2008) Pharmacologic targeting of a stem/progenitor population in vivo is associated with enhanced bone regeneration in mice. J Clin Invest 118(2):491–504PubMed

83.

De Matteo M, Brunetti AE, Maiorano E, Cafforio P, Dammacco F, Silvestris F Constitutive down-regulation of Osterix in osteoblasts from myeloma patients: in vitro effect of Bortezomib and Lenalidomide. Leukemia research 34(2):243–249

84.

Deleu S, Lemaire M, Arts J, Menu E, Van Valckenborgh E, Vande Broek I, De Raeve H, Coulton L, Van Camp B, Croucher P, Vanderkerken K (2009) Bortezomib alone or in combination with the histone deacetylase inhibitor JNJ-26481585: effect on myeloma bone disease in the 5T2MM murine model of myeloma. Cancer Res 69(13):5307–5311PubMedCrossRef

85.

Pennisi A, Li X, Ling W, Khan S, Zangari M, Yaccoby S (2009) The proteasome inhibitor, bortezomib suppresses primary myeloma and stimulates bone formation in myelomatous and nonmyelomatous bones in vivo. Am J Hematol 84(1):6–14PubMedCrossRef

86.

Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA (2008) Improved survival in multiple myeloma and the impact of novel therapies. Blood 111(5):2516–2520PubMedCrossRef

87.

Zangari M, Esseltine D, Lee CK, Barlogie B, Elice F, Burns MJ, Kang SH, Yaccoby S, Najarian K, Richardson P, Sonneveld P, Tricot G (2005) Response to bortezomib is associated to osteoblastic activation in patients with multiple myeloma. Br J Haematol 131(1):71–73PubMedCrossRef

88.

Terpos E, Heath DJ, Rahemtulla A, Zervas K, Chantry A, Anagnostopoulos A, Pouli A, Katodritou E, Verrou E, Vervessou EC, Dimopoulos MA, Croucher PI (2006) Bortezomib reduces serum dickkopf-1 and receptor activator of nuclear factor-kappaB ligand concentrations and normalises indices of bone remodelling in patients with relapsed multiple myeloma. Br J Haematol 135(5):688–692PubMedCrossRef

89.

Zangari M, Yaccoby S, Pappas L, Cavallo F, Kumar NS, Ranganathan S, Suva LJ, Gruenwald JM, Kern S, Zhan F, Esseltine D, Tricot G A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients. Haematologica 96(2):333–336

90.

Delforge M, Terpos E, Richardson PG, Shpilberg O, Khuageva NK, Schlag R, Dimopoulos MA, Kropff M, Spicka I, Petrucci MT, Samoilova OS, Mateos MV, Magen-Nativ H, Goldschmidt H, Esseltine DL, Ricci DS, Liu K, Deraedt W, Cakana A, van de Velde H, San Miguel JF (2011) Fewer bone disease events, improvement in bone remodelling, and evidence of bone healing with bortezomib plus melphalan-prednisone versus melphalan-prednisone, in the phase III VISTA trial in multiple myeloma. Eur J Haematol 86(5):372–384

91.

Terpos E, Kastritis E, Roussou M, Heath D, Christoulas D, Anagnostopoulos N, Eleftherakis-Papaiakovou E, Tsionos K, Croucher P, Dimopoulos MA (2008) The combination of bortezomib, melphalan, dexamethasone and intermittent thalidomide is an effective regimen for relapsed/refractory myeloma and is associated with improvement of abnormal bone metabolism and angiogenesis. Leukemia 22(12):2247–2256PubMedCrossRef

92.

Terpos E, Christoulas D, Kokkoris P, Gavriatopoulou M, Boutsikas G, Migkou M, Anargyrou K, Kastritis E, Tsionos K, Dimopoulos MA (2009) Increased bone mineral density in a subset of patients with relapsed multiple myeloma who received the combination of bortezomib, dexamethasone and zoledronic acid. Haematologica 94(suppl2):385, abs. 0958

93.

Pearsall RS, Canalis E, Cornwall-Brady M, Underwood KW, Haigis B, Ucran J, Kumar R, Pobre E, Grinberg A, Werner ED, Glatt V, Stadmeyer L, Smith D, Seehra J, Bouxsein ML (2008) A soluble activin type IIA receptor induces bone formation and improves skeletal integrity. Proc Natl Acad Sci U S A 105(19):7082–7087PubMedCrossRef

94.

Tassone P, Neri P, Carrasco DR, Burger R, Goldmacher VS, Fram R, Munshi V, Shammas MA, Catley L, Jacob GS, Venuta S, Anderson KC, Munshi NC (2005) A clinically relevant SCID-hu in vivo model of human multiple myeloma. Blood 106(2):713–716PubMedCrossRef

95.

Ruckle J, Jacobs M, Kramer W, Pearsall AE, Kumar R, Underwood KW, Seehra J, Yang Y, Condon CH, Sherman ML (2009) Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res 24(4):744–752PubMedCrossRef

96.

Abdulkadyrov K, Salogub G, Khuazheva N, Woolf R, Haltom E, Borgstein N, Knight R, Renshaw G, Yang Y, Sherman M (2009) ACE-011, a soluble activin receptor type iia igg-fc fusion protein, increases hemoglobin (Hb) and improves bone lesions in multiple myeloma patients receiving myelosuppressive chemotherapy: preliminary analysis. Blood: Abstract 749

97.

Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shalhoub V, Tipton B, Haldankar R, Chen Q, Winters A, Boone T, Geng Z, Niu QT, Ke HZ, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C (2009) Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res 24(4):578–588PubMedCrossRef

98.

Ominsky MS, Vlasseros F, Jolette J, Smith SY, Stouch B, Doellgast G, Gong J, Gao Y, Cao J, Graham K, Tipton B, Cai J, Deshpande R, Zhou L, Hale MD, Lightwood DJ, Henry AJ, Popplewell AG, Moore AR, Robinson MK, Lacey DL, Simonet WS, Paszty C Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res 25(5):948–959

99.

Padhi D, Jang G, Stouch B, Fang L, Posvar E Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 26(1):19–26

100.

Sukhdeo K, Mani M, Zhang Y, Dutta J, Yasui H, Rooney MD, Carrasco DE, Zheng M, He H, Tai YT, Mitsiades C, Anderson KC, Carrasco DR (2007) Targeting the beta-catenin/TCF transcriptional complex in the treatment of multiple myeloma. Proc Natl Acad Sci U S A 104(18):7516–7521PubMedCrossRef

101.

Choi SJ, Oba Y, Gazitt Y, Alsina M, Cruz J, Anderson J, Roodman GD (2001) Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease. J Clin Invest 108(12):1833–1841PubMed

102.

Oyajobi BO, Franchin G, Williams PJ, Pulkrabek D, Gupta A, Munoz S, Grubbs B, Zhao M, Chen D, Sherry B, Mundy GR (2003) Dual effects of macrophage inflammatory protein-1alpha on osteolysis and tumor burden in the murine 5TGM1 model of myeloma bone disease. Blood 102(1):311–319PubMedCrossRef

103.

Oyajobi B, Dairaghi D, Gupta A, McCluskey B, Wang Y, Seitz L, Powers J, Miao S, Zhang P, Schall T, Jaen J (2010) CCR1 blockade by an orally-available CCR1 antagonist reduces tumor burden and osteolysis in vivo in a mouse model of myeloma bone disease blood. Blood: Abstract 3000

104.

Liang M, Mallari C, Rosser M, Ng HP, May K, Monahan S, Bauman JG, Islam I, Ghannam A, Buckman B, Shaw K, Wei GP, Xu W, Zhao Z, Ho E, Shen J, Oanh H, Subramanyam B, Vergona R, Taub D, Dunning L, Harvey S, Snider RM, Hesselgesser J, Morrissey MM, Perez HD (2000) Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1. J Biol Chem 275(25):19000–19008PubMedCrossRef

105.

Reuss R, Schreiber V, Klein A, Infante-Duarte C, Filippi M, Pabst W, Pohl C, Oschmann P No significant effect of orally administered chemokine receptor 1 antagonist on intercellular adhesion molecule-3 expression in relapsing--remitting multiple sclerosis patients. Multiple sclerosis (Houndmills, Basingstoke, England) 16(3):366–369

106.

Clucas AT, Shah A, Zhang YD, Chow VF, Gladue RP (2007) Phase I evaluation of the safety, pharmacokinetics and pharmacodynamics of CP-481,715. Clin Pharmacokinet 46(9):757–766PubMedCrossRef

107.

Merritt JR, Liu J, Quadros E, Morris ML, Liu R, Zhang R, Jacob B, Postelnek J, Hicks CM, Chen W, Kimble EF, Rogers WL, O’Brien L, White N, Desai H, Bansal S, King G, Ohlmeyer MJ, Appell KC, Webb ML (2009) Novel pyrrolidine ureas as C-C chemokine receptor 1 (CCR1) antagonists. J Med Chem 52(5):1295–1301PubMedCrossRef

108.

Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, Hodsman AB, Eriksen EF, Ish-Shalom S, Genant HK, Wang O, Mitlak BH (2001) Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med 344(19):1434–1441PubMedCrossRef

109.

Pennisi A, Ling W, Li X, Khan S, Wang Y, Barlogie B, Shaughnessy JD, Jr., Yaccoby S Consequences of daily administered parathyroid hormone on myeloma growth, bone disease, and molecular profiling of whole myelomatous bone. PloS one 5(12):e15233

110.

Vallet S, Patel K, Cirstea D, Luly K, Pozzi S, Santo L, Eda H, Seehra J, Mahindra A, Scadden D, Raje N (2010) Lenalidomide in combination with the activin receptor type ii murine Fc protein RAP-011: preclinical rationale for a novel anti-myeloma strategy. Blood: Abstract 4075

Titel: Bone Anabolic Agents for the Treatment of Multiple Myeloma
verfasst von: Sonia Vallet
Noopur Raje
Publikationsdatum: 01.12.2011
Verlag: Springer Netherlands
Erschienen in: Cancer Microenvironment / Ausgabe 3/2011
Print ISSN: 1875-2292
Elektronische ISSN: 1875-2284
DOI: https://doi.org/10.1007/s12307-011-0090-7

Springer Medizin

Bone Anabolic Agents for the Treatment of Multiple Myeloma

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2011

Immunosuppressive Tumor Microenvironment in Cervical Cancer Patients

Targeting Bone as a Therapy for Myeloma

Angiogenesis and Multiple Myeloma

Introduction to the Special Issue on The Microenvironment of Bone Metastasis

Homing of Cancer Cells to the Bone

Matrix Metalloproteinases in Cytotoxic Lymphocytes Impact on Tumour Infiltration and Immunomodulation

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie