Proteasome inhibitor, bortezomib, for myeloma and lymphoma

Int J Clin Oncol. 2007 Oct;12(5):318-26. doi: 10.1007/s10147-007-0695-5. Epub 2007 Oct 22.

Abstract

Bortezomib, a boronic acid, is a potent and selective proteasome inhibitor. The 20S proteasome is an enzyme complex present in cells, and it degrades many cell-cycle control factors, signal transduction factors, transcription factors, and oncogene and anti-oncogene products, thus controlling cell proliferation, differentiation, and apoptosis. Bortezomib is a novel molecular targeting agent which was designed to exhibit an antitumor effect by selectively inhibiting the 20S proteasome. Multiple myeloma is one of the incurable B-cell malignancies that continues to relapse with current treatment modalities, and the duration to progression becomes shorter in patients who repeatedly receive chemotherapy. There are no available treatment options in which durable efficacy can be expected after relapse; therefore, an effective therapy with a novel mechanism of action has been desired. In this review article, the results of clinical trials of bortezomib for multiple myeloma, including a Japanese phase I/II and pharmacokinetic/pharmacodynamic study, and those for non-Hodgkin lymphoma, especially for mantle cell lymphoma, are summarized. In the Japanese phase I/II study of bortezomib for relapsed multiple myeloma, this agent showed remarkable efficacy, with acceptable toxicities and unique pharmacokinetic/pharmacodynamic profiles, warranting further investigations, including more relevant administration schedules.

Publication types

  • Review

MeSH terms

  • Animals
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Clinical Trials as Topic
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / enzymology
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / enzymology
  • Protease Inhibitors / therapeutic use*
  • Proteasome Inhibitors*
  • Pyrazines / therapeutic use*

Substances

  • Boronic Acids
  • Protease Inhibitors
  • Proteasome Inhibitors
  • Pyrazines
  • Bortezomib