The development of proteasome inhibitors as anticancer drugs

Cancer Cell. 2004 May;5(5):417-21. doi: 10.1016/s1535-6108(04)00120-5.


The ubiquitin-proteasome pathway plays a central role in the targeted destruction of cellular proteins, including cell cycle regulatory proteins. Because these pathways are critical for the proliferation and survival of all cells, and in particular cancerous cells, proteasome inhibition is a potentially attractive anticancer therapy. Based on encouraging cytotoxic activity, bortezomib was the first proteasome inhibitor to be evaluated in clinical trials. Efficacy and safety results from a phase 2 clinical trial contributed to approval of bortezomib for use in patients with relapsed and refractory multiple myeloma who have received at least 2 prior therapies and have demonstrated disease progression on their last therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Boronic Acids / therapeutic use*
  • Bortezomib
  • Clinical Trials as Topic
  • Humans
  • Multiple Myeloma / drug therapy*
  • Protease Inhibitors / therapeutic use*
  • Pyrazines / therapeutic use*
  • Ubiquitins / metabolism


  • Antineoplastic Agents
  • Boronic Acids
  • Protease Inhibitors
  • Pyrazines
  • Ubiquitins
  • Bortezomib