The introduction of the proteasome inhibitor bortezomib in 2003 significantly improved treatment of the B-cell malignancy MM (multiple myeloma). Relapse following bortezomib therapy is inevitable, however, and MM remains an incurable disease. In the present mini-review, we explore the mechanisms by which bortezomib resistance occurs in MM, including inherent and acquired mutation, and inducible pro-survival signalling. We also outline the importance of MM cell interaction with the BMSC (bone marrow stromal cell) microenvironment as a pro-survival mechanism, and examine some potential druggable targets within this milieu, such as IGFs (insulin-like growth factors) and Btk (Bruton's tyrosine kinase). Although our understanding of bortezomib resistance is far from complete, there are a number of scientific developments that can help inform clinical decisions in relapsed MM.
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Conference Article|
August 11 2014
Overcoming bortezomib resistance in multiple myeloma
Megan Y. Murray;
Megan Y. Murray
1
*Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U.K.
1To whom correspondence should be addressed (emailmegan.y.murray@uea.ac.uk).
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Martin J. Auger;
Martin J. Auger
†Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane, Norwich NR4 7UY, U.K.
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Kristian M. Bowles
Kristian M. Bowles
*Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U.K.
†Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane, Norwich NR4 7UY, U.K.
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Publisher: Portland Press Ltd
Received:
April 30 2014
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem Soc Trans (2014) 42 (4): 804–808.
Article history
Received:
April 30 2014
Citation
Megan Y. Murray, Martin J. Auger, Kristian M. Bowles; Overcoming bortezomib resistance in multiple myeloma. Biochem Soc Trans 1 August 2014; 42 (4): 804–808. doi: https://doi.org/10.1042/BST20140126
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