Targeting protein neddylation: A novel therapeutic strategy for the treatment of cancer

Meng Wang, Bruno C. Medeiros, Harry P. Erba, Daniel J. Deangelo, Francis J. Giles, Ronan T. Swords

Research output: Contribution to journalReview article

50 Scopus citations

Abstract

Introduction: The NEDD8 (neural precursor cell-expressed developmentally downregulated 8) conjugation pathway regulates the post-translational modification of oncogenic proteins. This pathway has important potential for cancer therapeutics. Several proteins vital in cancer biology are regulated by protein neddylation. These observations led to the development of a small molecule inhibitor that disrupts protein neddylation and leads to cancer cell death and important activity in early phase clinical trials. Areas covered: This review provides an extensive coverage of cellular protein homeostasis with particular emphasis on the NEDD8 conjugation pathway. Insights into a new investigational drug that specifically disrupts the NEDD8 pathway are discussed. The clinical data for this agent are also updated. Expert opinion: Neddylation controls key cellular pathways found to be dysregulated in many cancers. Protein neddylation is a relatively under-explored pathway for pharmacologic inhibition in cancer. Selective disruption of this pathway has demonstrated clinical activity in patients with myeloid neoplasms and is worth exploring further in combination with other anti-leukemia agents.

Original languageEnglish (US)
Pages (from-to)253-264
Number of pages12
JournalExpert Opinion on Therapeutic Targets
Volume15
Issue number3
DOIs
StatePublished - Mar 1 2011

Keywords

  • Acute myeloid leukemia
  • MLN4924
  • Neddylation
  • Therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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    Wang, M., Medeiros, B. C., Erba, H. P., Deangelo, D. J., Giles, F. J., & Swords, R. T. (2011). Targeting protein neddylation: A novel therapeutic strategy for the treatment of cancer. Expert Opinion on Therapeutic Targets, 15(3), 253-264. https://doi.org/10.1517/14728222.2011.550877