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The proteasome and proteasome inhibitors in cancer therapy

Peter M Voorhees1, Robert Z Orlowski

  • 1Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA. Peter_Voorhees@med.unc.edu

Annual Review of Pharmacology and Toxicology
|January 13, 2006
PubMed

Insights

Proteasome inhibitors, like bortezomib, show promise in treating cancers such as multiple myeloma and lymphoma. Research explores enhancing their efficacy and targeting resistance pathways for improved cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The proteasome is crucial for intracellular protein degradation.
  • Proteasome inhibitors demonstrate antitumor activity and are effective against multiple myeloma and non-Hodgkin lymphoma (NHL).
  • Proteasome inhibition can enhance other cancer therapeutics by downregulating chemoresistance.

Purpose of the Study:

  • To review the data supporting proteasome inhibitors in cancer therapy.
  • To outline strategies for enhancing proteasome inhibitor efficacy.
  • To discuss potential targets within the ubiquitin proteasome pathway for cancer treatment.

Main Methods:

  • Review of pharmacologic, preclinical, and clinical data on proteasome inhibitors.
  • Analysis of molecular mechanisms of resistance to proteasome inhibitors.
  • Identification of novel therapeutic targets, including the heat shock pathway.

Main Results:

  • Bortezomib, a proteasome inhibitor, shows significant efficacy in clinical trials for multiple myeloma and NHL.
  • Preclinical studies indicate that proteasome inhibition potentiates other cancer therapeutics.
  • Molecular characterization has identified resistance pathways and potential targets for overcoming them.

Conclusions:

  • Proteasome inhibitors are a valuable class of drugs for cancer therapy.
  • Strategies to enhance efficacy and overcome resistance are crucial for optimizing treatment.
  • Further exploration of the ubiquitin proteasome pathway may reveal new therapeutic targets.

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