title: Overcoming bortezomib resistance in multiple myeloma.
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.
authors.affiliation: *Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, U.K.
authors.forename: Megan Y
authors.initials: MY
authors.lastname: Murray
authors.affiliation: †Department of Haematology, Norfolk and Norwich University Hospitals NHS Trust, Colney Lane, Norwich NR4 7UY, U.K.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Auger
authors.forename: Kristian M
authors.initials: KM
authors.lastname: Bowles
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human