Emerging therapies targeting the ubiquitin proteasome system in cancer

J Clin Invest. 2014 Jan;124(1):6-12. doi: 10.1172/JCI71602. Epub 2014 Jan 2.


The ubiquitin proteasome system (UPS) is an essential metabolic constituent of cellular physiology that tightly regulates cellular protein concentrations with specificity and precision to optimize cellular function. Inhibition of the proteasome has proven very effective in the treatment of multiple myeloma, and this approach is being tested for utility in other malignancies. New pharmaceuticals targeting the proteasome itself or specific proximal pathways of the UPS are in development as antiproliferatives or immunomodulatory agents. In this article, we discuss the biology of UPS-targeting drugs, their use as therapy for neoplasia, and the state of clinical and preclinical development for emerging therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Molecular Targeted Therapy
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Proteasome Inhibitors / pharmacology
  • Proteasome Inhibitors / therapeutic use*
  • Ubiquitin-Protein Ligases / antagonists & inhibitors
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination*


  • Antineoplastic Agents
  • Immunologic Factors
  • Proteasome Inhibitors
  • Ubiquitin-Protein Ligases