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

Published

Journal Article (Review)

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.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.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.

Full Text

Duke Authors

Cited Authors

  • Wang, M; Medeiros, BC; Erba, HP; DeAngelo, DJ; Giles, FJ; Swords, RT

Published Date

  • March 2011

Published In

Volume / Issue

  • 15 / 3

Start / End Page

  • 253 - 264

PubMed ID

  • 21219242

Pubmed Central ID

  • 21219242

Electronic International Standard Serial Number (EISSN)

  • 1744-7631

International Standard Serial Number (ISSN)

  • 1472-8222

Digital Object Identifier (DOI)

  • 10.1517/14728222.2011.550877

Language

  • eng