{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:00:51Z","timestamp":1792789251711,"version":"4.5.0"},"reference-count":292,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"VeloSano Bike to Cure pilot award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergence of genetically heterogeneous sub-clones are the major causes of the relapsed-refractory state of MM. Cytopenias from cumulative treatment toxicity and disease refractoriness limit therapeutic options, hence creating an urgent need for innovative approaches effective against highly heterogeneous myeloma cell populations. Here, we present a comprehensive overview of the current and future treatment paradigm of MM, and highlight the gaps in therapeutic translations of recent advances in targeted therapy and immunotherapy. We also discuss the therapeutic potential of emerging preclinical research in multiple myeloma.<\/jats:p>","DOI":"10.3390\/cancers14174082","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T21:05:12Z","timestamp":1661288712000},"page":"4082","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Multiple Myeloma Therapy: Emerging Trends and Challenges"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-7975","authenticated-orcid":false,"given":"Danai","family":"Dima","sequence":"first","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Center for Immunotherapy and Precision Immuno-Oncology, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0375-8602","authenticated-orcid":false,"given":"Dongxu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Center for Immunotherapy and Precision Immuno-Oncology, Lerner Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1625-2881","authenticated-orcid":false,"given":"Divya Jyoti","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Center for Immunotherapy and Precision Immuno-Oncology, Lerner Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3403-7381","authenticated-orcid":false,"given":"Metis","family":"Hasipek","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haikoo S.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1991-1202","authenticated-orcid":false,"given":"Fauzia","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Khouri","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslaw P.","family":"Maciejewski","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-5255","authenticated-orcid":false,"given":"Babal K.","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH 44195, USA"},{"name":"Center for Immunotherapy and Precision Immuno-Oncology, Lerner Research Institute, Cleveland, OH 44195, USA"},{"name":"Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA"},{"name":"Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1056\/NEJMra1011442","article-title":"Multiple myeloma","volume":"364","author":"Palumbo","year":"2011","journal-title":"N. 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