title: Current Phase II investigational proteasome inhibitors for the treatment of multiple myeloma.
abstract: BACKGROUND
  The introduction and exploration of novel agents has significantly improved patient outcome in the treatment of multiple myeloma (MM). One such compound, bortezomib, was the first proteasome inhibitor (PI) to be approved as a MM therapeutic. The efficacy and safety data provided by bortezomib usage has provided the basis for the development of a second generation of PIs.
  
  
  METHODS
  This review focuses on PIs that are currently under evaluation in Phase II clinical trials for the treatment of MM. Furthermore, the article summarizes the currently understood mechanisms of action and the available clinical data for its use in MM.
  
  
  CONCLUSIONS
  Second generation PIs have demonstrated promising activity in patients with advanced-stage myeloma, including those refractory to bortezomib. It should be noted, however, that their efficacy in upfront settings is currently under investigation. Future PI development should include schedule optimization and the investigation of PIs potential synergistic activity with other anti-myeloma agents.
authors.affiliation: Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, University of Turin, Division of Hematology, Myeloma Unit , Via Genova 3, 10126 Torino , Italy +390116334198 ; +390116963737 ; sarabringhen@yahoo.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Bringhen
authors.forename: Francesca
authors.initials: F
authors.lastname: Gay
authors.forename: Francesca
authors.initials: F
authors.lastname: Donato
authors.forename: Rossella
authors.initials: R
authors.lastname: Troia
authors.forename: Roberto
authors.initials: R
authors.lastname: Mina
authors.forename: Antonio
authors.initials: A
authors.lastname: Palumbo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000069286:Bortezomib; D017322:Clinical Trials, Phase II as Topic; D015195:Drug Design; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D061988:Proteasome Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011719:Pyrazines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib
keywords: bortezomib; multiple myeloma; novel agents; proteasome inhibitors