{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T07:01:57Z","timestamp":1777878117218,"version":"3.51.4"},"reference-count":125,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2011,7,6]],"date-time":"2011-07-06T00:00:00Z","timestamp":1309910400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Hematology"],"published-print":{"date-parts":[[2011,8]]},"abstract":"<jats:p>Myeloma therapy has undergone significant advances in recent years resulting in a marked improvement in survival. Knowledge of the active pathways involved in myeloma pathogenesis has led to the discovery of novel agents\u2009and greatly expanded the potential armamentarium available for treatment. This better understanding of the disease and resistance mechanisms has resulted in new agent classes that are being evaluated in preclinical and early clinical studies. In addition, dosing for existing agents is being optimized, and they are being given in new combinations. In this article, we review experimental agents that are showing promise in multiple myeloma treatment. New biological agents in clinical trials hold the promise of efficacy through novel mechanisms of action, with a significant reduction of dose-limiting toxicities compared with classic cytotoxic chemotherapeutics. Second-generation proteasome inhibitors and immunomodulatory agents are furthest along in clinical development, and histone deacetylase inhibitors, heat shock protein 90 inhibitors, Akt inhibitors and monoclonal antibodies are some of the other agents entering later-phase clinical trials. We also review developments in targeting the myeloma stem cell as an exciting new treatment direction.<\/jats:p>","DOI":"10.1177\/2040620711410097","type":"journal-article","created":{"date-parts":[[2011,7,7]],"date-time":"2011-07-07T00:14:09Z","timestamp":1309997649000},"page":"213-230","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Experimental approaches in the treatment of multiple myeloma"],"prefix":"10.1177","volume":"2","author":[{"given":"Saad A.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam D.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2011,7,6]]},"reference":[{"key":"bibr1-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1361"},{"key":"bibr2-2040620711410097","first-page":"2870","volume":"114","author":"Agura E.","year":"2009","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr3-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-08-3450"},{"key":"bibr4-2040620711410097","doi-asserted-by":"crossref","unstructured":"Badros, A., Burger, A.M., Philip, S., Niesvizky, R., Kolla, S.S., Goloubeva, O.\n                      et al\n                      . (2009) Phase I study of vorinostat in combination with bortezomib for relapsed and refractory multiple myeloma.\n                      Clin Cancer Res\n                      15: 5250\u20135257.","DOI":"10.1158\/1078-0432.CCR-08-2850"},{"key":"bibr5-2040620711410097","doi-asserted-by":"crossref","unstructured":"Badros, A. Z., Vij, R., Martin, T., Zonder, J. A., Wong, A. F., Woo, T.\n                      et al\n                      . (2010) Phase II study of carfilzomib in patients with relapsed\/refractory multiple myeloma and renal insufficiency.\n                      J Clin Oncol\n                      (ASCO Annual Meeting Abstracts) 28: 8128.","DOI":"10.1200\/jco.2010.28.15_suppl.8128"},{"key":"bibr6-2040620711410097","first-page":"706","volume":"90","author":"Bataille R.","year":"2005","journal-title":"Haematologica"},{"key":"bibr7-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2781"},{"key":"bibr8-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-1098"},{"key":"bibr9-2040620711410097","first-page":"616","volume":"11","author":"Bennett M.K.","year":"2008","journal-title":"Curr Opin Drug Discov Devel"},{"key":"bibr10-2040620711410097","first-page":"3575","volume":"108","author":"Bensinger W.","year":"2006","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr11-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2010.28.15_suppl.8029"},{"key":"bibr12-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-01-0034"},{"key":"bibr13-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-009-0531-7"},{"key":"bibr14-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-07-294983"},{"key":"bibr15-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2009.01384.x"},{"key":"bibr16-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-09-0499"},{"key":"bibr17-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.52.1"},{"key":"bibr18-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-04-016055"},{"key":"bibr19-2040620711410097","first-page":"1962","volume":"116","author":"Chanan-Khan A.","year":"2010","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr20-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.10.013"},{"key":"bibr21-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-276626"},{"key":"bibr22-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4086"},{"key":"bibr23-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4489"},{"key":"bibr24-2040620711410097","first-page":"2847","volume":"114","author":"Flint O.P.","year":"2009","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr25-2040620711410097","first-page":"990","volume":"116","author":"Ghobrial I.M.","year":"2010","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr26-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.08.005"},{"key":"bibr27-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-279893"},{"key":"bibr28-2040620711410097","doi-asserted-by":"crossref","unstructured":"Harousseau, J.L., Palumbo, A., Richardson, P.G., Schlag, R., Dimopoulos, M.A., Shpilberg, O.\n                      et al\n                      . (2010) Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 vista study of bortezomib plus melphalan-prednisone versus melphalan-prednisone.\n                      Blood\n                      116: 3743\u20133750.","DOI":"10.1182\/blood-2010-03-275800"},{"key":"bibr29-2040620711410097","doi-asserted-by":"publisher","DOI":"10.2217\/14796694.3.6.639"},{"key":"bibr30-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04322.x"},{"key":"bibr31-2040620711410097","doi-asserted-by":"crossref","unstructured":"Hideshima, T., Chauhan, D., Shima, Y., Raje, N., Davies, F.E., Tai, Y.T.\n                      et al\n                      . 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(2003) Heat shock protein 90 as a molecular target for cancer therapeutics.\n                      Cancer Cell\n                      . 2003 Mar; 3(3): 213\u2013217.","DOI":"10.1016\/S1535-6108(03)00029-1"},{"key":"bibr40-2040620711410097","first-page":"3060","volume":"116","author":"Jagannath S.","year":"2010","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr41-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05540.x"},{"key":"bibr42-2040620711410097","first-page":"3023","volume":"116","author":"Jakubowiak A.J.","year":"2010","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr43-2040620711410097","first-page":"862","volume":"116","author":"Jakubowiak A.J.","year":"2010","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr44-2040620711410097","first-page":"3064","volume":"116","author":"Jakubowiak A.J.","year":"2010","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr45-2040620711410097","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20073"},{"key":"bibr46-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07024.x"},{"key":"bibr47-2040620711410097","first-page":"8593","volume":"27","author":"Kaufman J.L.","year":"2009","journal-title":"J Clin Oncol (ASCO Annual Meeting Abstracts)"},{"key":"bibr48-2040620711410097","first-page":"3013","volume":"116","author":"Kong S.-Y.","year":"2010","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr49-2040620711410097","doi-asserted-by":"crossref","unstructured":"Kuhn, D.J., Chen, Q., Voorhees, P.M., Strader, J.S., Shenk, K.D., Sun, C.M.\n                      et al\n                      . 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(2006) Antimyeloma activity of heat shock protein-90 inhibition.\n                      Blood\n                      107: 1092\u20131100.","DOI":"10.1182\/blood-2005-03-1158"},{"key":"bibr71-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5725"},{"key":"bibr72-2040620711410097","first-page":"1166","volume":"110","author":"Moreau P.","year":"2007","journal-title":"Blood (ASH Annual Meeting Abstracts)"},{"key":"bibr73-2040620711410097","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-3112"},{"key":"bibr74-2040620711410097","doi-asserted-by":"crossref","unstructured":"Nawrocki, S.T., Carew, J.S., Pino, M.S., Highshaw, R. A., Andtbacka, R. H., Dunner Jr, K.\n                      et al\n                      . 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