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memo - Magazine of European Medical Oncology
Erschienen in:

01.12.2014 | short review

Angiogenesis inhibition, hypoxia, and targeting the bone marrow microenvironment in multiple myeloma: new strategies and targets

verfasst von: Normann Steiner, MD, Johann Kern, PhD, Gerold Untergasser, PhD, Univ.-Doz. Eberhard Gunsilius

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 4/2014

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Abstract

Multiple myeloma (MM) is a hematological B-cell malignancy that has still a fatal prognosis. Although the treatments have improved, one major problem in MM is the clinical resistance to available drugs and combination therapies over time. Novel agents, such as oral proteasome inhibitors, monoclonal antibodies, second generation immunomodulatory drugs and therapies targeting the cell signaling and the tumor microenvironment are in development for the treatment of relapsed/refractory MM. In this review, we refer on the role of new strategies targeting the tumor microenvironment, especially on angiogenesis, hypoxia and other interactions between MM and bone marrow components.
Vorheriger Artikel Contribution of the vascular bone marrow niche to leukemia progression
Nächster Artikel Angiogenesis in myeloproliferative neoplasms, new markers and future directions
Literatur
1.
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–28.PubMedCrossRef
2.
3.
Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28(5):1122–8.PubMedCentralPubMedCrossRef
4.
5.
6.
Fowler JA, Mundy GR, Lwin ST, Edwards CM. Bone marrow stromal cells create a permissive microenvironment for myeloma development: a new stromal role for Wnt Inhibitor Dkk1. Cancer Res. 2012;72(9):2183–9.PubMedCentralPubMedCrossRef
7.
Romano A, Conticello C, Cavalli M, Vetro C, La Fauci A, Parrinello NL, et al. Immunological dysregulation in multiple myeloma microenvironment. Biomed Res Int. 2014;2014:198539.PubMedCentralPubMed
8.
9.
de la Puente P, Muz B, Azab F, Azab AK. Cell trafficking of endothelial progenitor cells in tumor progression. Clin Cancer Res. 2013;19(13):3360–8.CrossRef
10.
Vacca A, Ribatti D. Bone marrow angiogenesis in multiple myeloma. Leukemia. 2006;20(2):193–9.PubMedCrossRef
11.
Di Raimondo F, Azzaro MP, Palumbo G, Bagnato S, Giustolisi G, Floridia P, et al. Angiogenic factors in multiple myeloma: higher levels in bone marrow than in peripheral blood. Haematologica. 2000;85(8):800–5.PubMed
12.
Du W, Hattori Y, Hashiguchi A, Kondoh K, Hozumi N, Ikeda Y, et al. Tumor angiogenesis in the bone marrow of multiple myeloma patients and its alteration by thalidomide treatment. Pathol Int. 2004;54(5):285–94.PubMedCrossRef
13.
Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B, et al. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009;2:36.PubMedCentralPubMedCrossRef
14.
Kumar S, Witzig TE, Dispenzieri A, Lacy MQ, Wellik LE, Fonseca R, et al. Effect of thalidomide therapy on bone marrow angiogenesis in multiple myeloma. Leukemia. 2004;18(3):624–7.PubMedCrossRef
15.
Zangari M, Anaissie E, Stopeck A, Morimoto A, Tan N, Lancet J, et al. Phase II Study of SU5416, a small molecule vascular endothelial growth factor tyrosine kinase receptor inhibitor, in patients with refractory multiple myeloma. Clin Cancer Res. 2004;10(1):88–95.PubMedCrossRef
16.
Podar K, Catley LP, Tai YT, Shringarpure R, Carvalho P, Hayashi T, et al. GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment. Blood. 2004;103(9):3474–9.PubMedCrossRef
17.
Kovacs M, Reece D, Marcellus D, Meyer R, Mathews S, Dong RP, et al. A phase II study of ZD6474 (Zactima), a selective inhibitor of VEGFR and EGFR tyrosine kinase in patients with relapsed multiple myeloma—NCIC CTG IND.145. Invest New Drugs. 2006;24(6):529–35.PubMed
18.
Prince HM, Hönemann D, Spencer A, Rizzieri DA, Stadtmauer EA, Roberts AW, et al. Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034). Blood. 2009;113:4819–20.PubMedCrossRef
19.
Van Meter ME, Kim ES. Bevacizumab: current updates in treatment. Curr Opin Oncol. 2010;22(6):586–91.PubMedCrossRef
20.
Somlo G, Lashkari A, Bellamy W, Zimmerman TM, Tuscano JM, O'Donnell MR, et al. Phase II randomized trial of bevacizumab versus bevacizumab and thalidomide for relapsed/refractory multiple myeloma: a California Cancer Consortium trial. Br J Haematol. 2011;154(4):533–5.PubMedCentralPubMedCrossRef
21.
Raschko M, Markovina S, Miyamoto S, Longo W, Williams E, McFarland T, et al. Phase II trial of bevacizumab combined with low dose dexamethasone and lenalidomide (BEV/REV/DEX) for relapsed or refractory myeloma (MM). ASH Annu Meet Abstracts. 2007;110(11):1173.
22.
Azab AK, Hu J, Quang P, Azab F, Pitsillides C, Awwad R, et al. Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features. Blood. 2012;119(24):5782–94.PubMedCentralPubMedCrossRef
23.
Alsayed Y, Ngo H, Runnels J, Leleu X, Singha UK, Pitsillides CM, et al. Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma. Blood. 2007;109(7):2708–17.PubMedCentralPubMed
24.
Azab AK, Runnels JM, Pitsillides C, Moreau AS, Azab F, Leleu X, et al. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood. 2009;113(18):4341–51.PubMedCentralPubMedCrossRef
25.
Ghobrial IM, Shain K, Hanlon C, Banwait R, Azab AK, Laubach JP, et al. Phase I/II Trial of Plerixafor and Bortezomib As a Chemosensitization Strategy In Relapsed Or Relapsed/Refractory Multiple Myeloma. Annual Meeting of American Society of Hematology 2013. Blood;122(21):1947a.
26.
Ludwig H, Weisel K, Engelhardt M, Greil R, Cafro AM, Petrucci MT et al. Anti-CXCL12/SDF-1 Spiegelmer® Nox-A12 Alone and In Combination With Bortezomib and Dexamethasone In Patients With Relapsed Multiple Myeloma: Results From A Phase IIa Study. Annual Meeting of American Society of Hematology 2013. Blood;122(21):1951.
27.
Ria R, Catacchio I, Berardi S, De Luisi A, Caivano A, Piccoli C, et al. HIF-1α of bone marrow endothelial cells implies relapse and drug resistance in patients with multiple myeloma and may act as a therapeutic target. Clin Cancer Res. 2014;20(4):847–58.PubMedCrossRef
28.
Storti P, Bolzoni M, Donofrio G, Airoldi I, Guasco D, Toscani D, et al. Hypoxia-inducible factor (HIF)-1alpha suppression in myeloma cells blocks tumoral growth in vivo inhibiting angiogenesis and bone destruction. Leukemia. 2013;27(8):1697–706.PubMedCrossRef
29.
Azab AK, Quang P, Azab F, Pitsillides C, Thompson B, Chonghaile T, et al. P-selectin glycoprotein ligand regulates the interaction of multiple myeloma cells with the bone marrow microenvironment. Blood. 2012;119(6):1468–78.PubMedCentralPubMedCrossRef
30.
Kibler C, Schermutzki F, Waller HD, Timpl R, Muller CA, Klein G. Adhesive interactions of human multiple myeloma cell lines with different extracellular matrix molecules. Cell Adhes Commun. 1998;5(4):307–23.PubMedCrossRef
31.
Liebisch P, Eppinger S, Schopflin C, Stehle G, Munzert G, Dohner H, et al. CD44v6, a target for novel antibody treatment approaches, is frequently expressed in multiple myeloma and associated with deletion of chromosome arm 13q. Haematologica. 2005;90(4):489–93.PubMed
32.
Roccaro AM, Hideshima T, Raje N, Kumar S, Ishitsuka K, Yasui H, et al. Bortezomib mediates antiangiogenesis in multiple myeloma via direct and indirect effects on endothelial cells. Cancer Res. 2006;66(1):184–91.PubMedCrossRef
33.
Kern J, Untergasser G, Zenzmaier C, Sarg B, Gastl G, Gunsilius E, et al. GRP-78 secreted by tumor cells blocks the antiangiogenic activity of bortezomib. Blood. 2009;114(18):3960–7.PubMedCrossRef
34.
Caers J, Menu E, De Raeve H, Lepage D, Van Valckenborgh E, Van Camp B, et al. Antitumour and antiangiogenic effects of Aplidin in the 5TMM syngeneic models of multiple myeloma. Br J Cancer. 2008;98(12):1966–74.PubMedCentralPubMedCrossRef
35.
Mitsiades CS, Ocio EM, Pandiella A, Maiso P, Gajate C, Garayoa M, et al. Aplidin, a marine organism-derived compound with potent antimyeloma activity in vitro and in vivo. Cancer Res. 2008;68(13):5216–25.PubMedCrossRef
36.
Broggini M, Marchini SV, Galliera E, Borsotti P, Taraboletti G, Erba E, et al. Aplidine, a new anticancer agent of marine origin, inhibits vascular endothelial growth factor (VEGF) secretion and blocks VEGF-VEGFR-1 (flt-1) autocrine loop in human leukemia cells MOLT-4. Leukemia. 2003;17(1):52–9.PubMedCrossRef
37.
Deryugina EI, Quigley JP. Chick embryo chorioallantoic membrane model systems to study and visualize human tumor cell metastasis. Histochem Cell Biol. 2008;130(6):1119–30.PubMedCentralPubMedCrossRef
Metadaten
Titel
Angiogenesis inhibition, hypoxia, and targeting the bone marrow microenvironment in multiple myeloma: new strategies and targets
verfasst von
Normann Steiner, MD
Johann Kern, PhD
Gerold Untergasser, PhD
Univ.-Doz. Eberhard Gunsilius
Publikationsdatum
01.12.2014
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 4/2014
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-014-0184-2

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