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Targeting the Pim kinases in multiple myeloma
Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in M...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526774/ https://www.ncbi.nlm.nih.gov/pubmed/26186558 http://dx.doi.org/10.1038/bcj.2015.46 |
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author | Keane, N A Reidy, M Natoni, A Raab, M S O'Dwyer, M |
author_facet | Keane, N A Reidy, M Natoni, A Raab, M S O'Dwyer, M |
author_sort | Keane, N A |
collection | PubMed |
description | Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and/or with novel drugs targeting other survival pathways in MM. |
format | Online Article Text |
id | pubmed-4526774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45267742015-08-06 Targeting the Pim kinases in multiple myeloma Keane, N A Reidy, M Natoni, A Raab, M S O'Dwyer, M Blood Cancer J Review Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and/or with novel drugs targeting other survival pathways in MM. Nature Publishing Group 2015-07 2015-07-17 /pmc/articles/PMC4526774/ /pubmed/26186558 http://dx.doi.org/10.1038/bcj.2015.46 Text en Copyright © 2015 Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Review Keane, N A Reidy, M Natoni, A Raab, M S O'Dwyer, M Targeting the Pim kinases in multiple myeloma |
title | Targeting the Pim kinases in multiple myeloma |
title_full | Targeting the Pim kinases in multiple myeloma |
title_fullStr | Targeting the Pim kinases in multiple myeloma |
title_full_unstemmed | Targeting the Pim kinases in multiple myeloma |
title_short | Targeting the Pim kinases in multiple myeloma |
title_sort | targeting the pim kinases in multiple myeloma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526774/ https://www.ncbi.nlm.nih.gov/pubmed/26186558 http://dx.doi.org/10.1038/bcj.2015.46 |
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