title: Novel agents derived from the currently approved treatments for MM: novel proteasome inhibitors and novel IMIDs.
abstract: BACKGROUND
  Several novel proteasome inhibitors (PIs) and immunomodulatory agents (IMIDs) with similar, but not exactly the same, mechanisms of action than their predecessors have been developed in the last years with three different aims: to increase the efficacy; to overcome the resistance and to exhibit a better toxicity profile.
  
  
  METHODS
  This review summarizes the mechanism of action of novel PIs (carfilzomib, ONX-0912, MLN-9708, marizomib and CEP-18770) and IMIDs (pomalidomide), stressing the similarities and differences with their parental drugs. It also reviews their most updated clinical results. A search of the recent literature in published papers and abstracts from the most important oncology scientific meetings (ASCO and ASH) has been performed.
  
  
  CONCLUSIONS
  Novel PIs and IMIDs show clinical activity as single agents and in combination with dexamethasone, with similar or even higher efficacy than their predecessors; moreover, they may even overcome resistance to their parental drugs, indicating that there are some differences in their mechanisms of action and resistance. The investigation of these mechanisms of resistance and ways to overcome it would allow the optimization of the sequential use of these agents, and the design of novel therapeutic strategies and more appropriate scientifically based combinations.
authors.affiliation: University of Salamanca, University Hospital & Cancer Research Center, Department of Hematology, Salamanca, Spain. emocio@usal.es
authors.forename: Enrique M
authors.initials: EM
authors.lastname: Ocio
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San-Miguel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000201:enzymology; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; D011480:Protease Inhibitors; D046988:Proteasome Endopeptidase Complex