Overcoming bortezomib resistance in multiple myeloma

Author:

Murray Megan Y.1,Auger Martin J.2,Bowles Kristian M.12

Affiliation:

1. Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U.K.

2. Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane, Norwich NR4 7UY, U.K.

Abstract

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.

Publisher

Portland Press Ltd.

Subject

Biochemistry

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