Emerging therapies targeting the ubiquitin proteasome system in cancer.

Abstract

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.

• Authors: Nathaniel M Weathington, Rama K Mallampalli
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 124 Issue 1 Pg. 6-12 (Jan 2014) ISSN: 1558-8238 [Electronic] United States
• PMID: 24382383 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

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

Topics

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