title: Bortezomib for the treatment of non-Hodgkin's lymphoma.
abstract: BACKGROUND
  Bortezomib , the first proteasome inhibitor (PI) to be evaluated in humans, is approved in the USA and Europe for the treatment of patients with multiple myeloma, and in the USA for patients with relapsed mantle cell lymphoma (MCL).
  
  
  METHODS
  This review examines the role of bortezomib in the therapy of non-Hodgkin's lymphoma (NHL). Bortezomib may be particularly effective against the NF-κB-dependent activated B-cell subtype of diffuse large B-cell lymphoma. The combination of bortezomib with rituximab and dexamethasone represents a standard approach for the treatment of Waldenström's macroglobulinemia, and that with bendamustine and rituximab has demonstrated excellent efficacy in follicular lymphoma. Combinations with other novel agents, such as inhibitors of cyclin-dependent kinases or histone deacetylases, also hold substantial promise in NHL. Unmet needs in NHL, competitor compounds, chemistry, pharmacokinetics, pharmacodynamics and safety and tolerability of bortezomib are also discussed.
  
  
  CONCLUSIONS
  The success of bortezomib in MCL has validated the proteasome as a therapeutic target in NHL. Rational combinations, for example, with Bruton's tyrosine kinase inhibitors or BH3-mimetics, may hold the key to optimizing the therapeutic potential of PIs in NHL. Future trials are likely to involve newer agents with improved pharmacodynamic (e.g., carfilzomib, marizomib) or pharmacokinetic (e.g., ixazomib, oprozomib) properties.
authors.affiliation: Virginia Commonwealth University, Massey Cancer Center , Richmond, VA , USA.
authors.forename: Prithviraj
authors.initials: P
authors.lastname: Bose
authors.forename: Michael S
authors.initials: MS
authors.lastname: Batalo
authors.forename: Beata
authors.initials: B
authors.lastname: Holkova
authors.forename: Steven
authors.initials: S
authors.lastname: Grant
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001897:Boronic Acids / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D009101:Multiple Myeloma / Q000188:drug therapy; D061988:Proteasome Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D011719:Pyrazines / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib
keywords: Waldenström’s macroglobulinemia; bortezomib; cutaneous T-cell lymphoma; diffuse large B-cell lymphoma; follicular lymphoma; mantle cell lymphoma; marginal zone lymphoma; non-Hodgkin’s lymphoma; peripheral T-cell lymphoma