Proteasome inhibitors as new anticancer drugs

Curr Opin Oncol. 2002 Nov;14(6):628-34. doi: 10.1097/00001622-200211000-00007.


The targeted degradation of key regulatory proteins is an essential element of cell cycle control. The proteasome plays a central role in the degradation of such proteins and has therefore become an important therapeutic target for diseases involving cell proliferation, notably cancer. This review summarizes numerous studies demonstrating that proteasome inhibition induces apoptosis and sensitizes cancer cells to traditional tumoricidal agents both and The potent and selective proteasome inhibitor, PS-341, is particularly promising from a therapeutic perspective, and it is the only such inhibitor that has progressed to clinical trials. Preliminary data indicate that the drug is well tolerated by patients with cancer, and further trials are underway to assess the safety and efficacy of proteasome inhibition in hematologic and solid tumors, both as a monotherapy and in combination with other chemotherapeutics.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols
  • Apoptosis / drug effects*
  • Boronic Acids / pharmacology*
  • Bortezomib
  • Cell Cycle Proteins / pharmacology
  • Clinical Trials as Topic
  • Cysteine Endopeptidases / pharmacology*
  • Disease Models, Animal
  • Humans
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / pharmacology*
  • Protease Inhibitors / pharmacology*
  • Proteasome Endopeptidase Complex
  • Pyrazines / pharmacology*
  • Rats
  • Transcription Factors / pharmacology
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Boronic Acids
  • Cell Cycle Proteins
  • Multienzyme Complexes
  • Protease Inhibitors
  • Pyrazines
  • Transcription Factors
  • Bortezomib
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex