Current Hematologic Malignancy Reports

, Volume 7, Issue 4, pp 258–266

New Proteasome Inhibitors in Myeloma

  • Panisinee Lawasut
  • Dharminder Chauhan
  • Jacob Laubach
  • Catriona Hayes
  • Claire Fabre
  • Michelle Maglio
  • Constantine Mitsiades
  • Teru Hideshima
  • Kenneth C. Anderson
  • Paul G. Richardson
Multiple Myeloma (V Rajkumar, Section Editor)

DOI: 10.1007/s11899-012-0141-2

Cite this article as:
Lawasut, P., Chauhan, D., Laubach, J. et al. Curr Hematol Malig Rep (2012) 7: 258. doi:10.1007/s11899-012-0141-2

Abstract

Proteasome inhibition has a validated role in cancer therapy since the successful introduction of bortezomib for the treatment of multiple myeloma (MM) and mantle cell lymphoma, leading to the development of second-generation proteasome inhibitors (PI) for MM patients in whom currently approved therapies have failed. Five PIs have reached clinical evaluation, with the goals of improving efficacy and limiting toxicity, including peripheral neuropathy (PN). Carfilzomib, an epoxyketone with specific chymothrypsin-like activity, acts as an irreversible inhibitor and was recently FDA approved for the response benefit seen in relapsed and refractory MM patients previously treated with bortezomib, thalidomide and lenalidomide. ONX-0912 is now under evaluation as an oral form with similar activity. The boronate peptides MLN9708 and CEP-18770 are orally bioactive bortezomib analogs with prolonged activity and greater tissue penetration. NPI-0052 (marizomib) is a unique, beta-lactone non-selective PI that has been shown to potently overcome bortezomib resistance in vitro. All of these second-generation PIs demonstrate encouraging anti-MM activity and appear to reduce the incidence of PN, with clinical trials ongoing.

Keywords

Second generation proteasome inhibitorsProteasome inhibitorsMyelomaMLN9708MLN2238IxazomibCEP-18770DelanzomibCarfilzomibPR-171OprozomibONX 0912PR-047NPI-0052MarizomibSalinosporamide

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Panisinee Lawasut
    • 1
    • 2
  • Dharminder Chauhan
    • 1
  • Jacob Laubach
    • 1
  • Catriona Hayes
    • 1
  • Claire Fabre
    • 1
    • 3
  • Michelle Maglio
    • 1
  • Constantine Mitsiades
    • 1
  • Teru Hideshima
    • 1
  • Kenneth C. Anderson
    • 1
  • Paul G. Richardson
    • 1
  1. 1.Division of Hematologic Oncology, Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer InstituteHarvard Medical SchoolBostonUSA
  2. 2.Division of Hematology, Department of Medicine, Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross SocietyBangkokThailand
  3. 3.Department of Medical OncologyCurie InstituteParisFrance