Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche
Multiple myeloma (MM) is still an incurable disease, despite considerable improvements in treatment strategies, as resistance to most currently available agents is not uncommon. In this study, data on drug resistance in MM were analyzed and led to the following conclusions: resistance occurs via int...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.973836/full |
| _version_ | 1811183695781953536 |
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| author | Antonio Giovanni Solimando Antonio Giovanni Solimando Eleonora Malerba Patrizia Leone Marcella Prete Carolina Terragna Michele Cavo Vito Racanelli |
| author_facet | Antonio Giovanni Solimando Antonio Giovanni Solimando Eleonora Malerba Patrizia Leone Marcella Prete Carolina Terragna Michele Cavo Vito Racanelli |
| author_sort | Antonio Giovanni Solimando |
| collection | DOAJ |
| description | Multiple myeloma (MM) is still an incurable disease, despite considerable improvements in treatment strategies, as resistance to most currently available agents is not uncommon. In this study, data on drug resistance in MM were analyzed and led to the following conclusions: resistance occurs via intrinsic and extrinsic mechanisms, including intraclonal heterogeneity, drug efflux pumps, alterations of drug targets, the inhibition of apoptosis, increased DNA repair and interactions with the bone marrow (BM) microenvironment, cell adhesion, and the release of soluble factors. Since MM involves the BM, interactions in the MM-BM microenvironment were examined as well, with a focus on the cross-talk between BM stromal cells (BMSCs), adipocytes, osteoclasts, osteoblasts, endothelial cells, and immune cells. Given the complex mechanisms that drive MM, next-generation treatment strategies that avoid drug resistance must target both the neoplastic clone and its non-malignant environment. Possible approaches based on recent evidence include: (i) proteasome and histone deacetylases inhibitors that not only target MM but also act on BMSCs and osteoclasts; (ii) novel peptide drug conjugates that target both the MM malignant clone and angiogenesis to unleash an effective anti-MM immune response. Finally, the role of cancer stem cells in MM is unknown but given their roles in the development of solid and hematological malignancies, cancer relapse, and drug resistance, their identification and description are of paramount importance for MM management. |
| first_indexed | 2024-04-11T09:51:16Z |
| format | Article |
| id | doaj.art-e63e1f19b52240be80f01d26c41eae2b |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-11T09:51:16Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e63e1f19b52240be80f01d26c41eae2b2022-12-22T04:30:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-09-011210.3389/fonc.2022.973836973836Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow nicheAntonio Giovanni Solimando0Antonio Giovanni Solimando1Eleonora Malerba2Patrizia Leone3Marcella Prete4Carolina Terragna5Michele Cavo6Vito Racanelli7Department of Biomedical Sciences and Human Oncology, School of Medicine, ‘Aldo Moro’ University of Bari, Bari, ItalyIstituto di ricovero e cura a carattere scientifico (IRCCS) Istituto Tumori ‘Giovanni Paolo II’ of Bari, Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, School of Medicine, ‘Aldo Moro’ University of Bari, Bari, ItalyDepartment of Biomedical Sciences and Human Oncology, School of Medicine, ‘Aldo Moro’ University of Bari, Bari, ItalyDepartment of Interdisciplinary Medicine, School of Medicine, ‘Aldo Moro’ University of Bari, Bari, Italy’Seràgnoli’ Institute of Hematology, Bologna University School of Medicine, Bologna, Italy’Seràgnoli’ Institute of Hematology, Bologna University School of Medicine, Bologna, ItalyDepartment of Interdisciplinary Medicine, School of Medicine, ‘Aldo Moro’ University of Bari, Bari, ItalyMultiple myeloma (MM) is still an incurable disease, despite considerable improvements in treatment strategies, as resistance to most currently available agents is not uncommon. In this study, data on drug resistance in MM were analyzed and led to the following conclusions: resistance occurs via intrinsic and extrinsic mechanisms, including intraclonal heterogeneity, drug efflux pumps, alterations of drug targets, the inhibition of apoptosis, increased DNA repair and interactions with the bone marrow (BM) microenvironment, cell adhesion, and the release of soluble factors. Since MM involves the BM, interactions in the MM-BM microenvironment were examined as well, with a focus on the cross-talk between BM stromal cells (BMSCs), adipocytes, osteoclasts, osteoblasts, endothelial cells, and immune cells. Given the complex mechanisms that drive MM, next-generation treatment strategies that avoid drug resistance must target both the neoplastic clone and its non-malignant environment. Possible approaches based on recent evidence include: (i) proteasome and histone deacetylases inhibitors that not only target MM but also act on BMSCs and osteoclasts; (ii) novel peptide drug conjugates that target both the MM malignant clone and angiogenesis to unleash an effective anti-MM immune response. Finally, the role of cancer stem cells in MM is unknown but given their roles in the development of solid and hematological malignancies, cancer relapse, and drug resistance, their identification and description are of paramount importance for MM management.https://www.frontiersin.org/articles/10.3389/fonc.2022.973836/fullmultiple myelomadrug resistancebone marrow microenvironmentmonoclonal gammopathy of undetermined significancetherapeutic targets |
| spellingShingle | Antonio Giovanni Solimando Antonio Giovanni Solimando Eleonora Malerba Patrizia Leone Marcella Prete Carolina Terragna Michele Cavo Vito Racanelli Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche Frontiers in Oncology multiple myeloma drug resistance bone marrow microenvironment monoclonal gammopathy of undetermined significance therapeutic targets |
| title | Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche |
| title_full | Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche |
| title_fullStr | Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche |
| title_full_unstemmed | Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche |
| title_short | Drug resistance in multiple myeloma: Soldiers and weapons in the bone marrow niche |
| title_sort | drug resistance in multiple myeloma soldiers and weapons in the bone marrow niche |
| topic | multiple myeloma drug resistance bone marrow microenvironment monoclonal gammopathy of undetermined significance therapeutic targets |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.973836/full |
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