title: Targeting protein neddylation: a novel therapeutic strategy for the treatment of cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cambridge University, Medicine, Cambridge, UK.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Medeiros
authors.forename: Harry P
authors.initials: HP
authors.lastname: Erba
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: DeAngelo
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Giles
authors.forename: Ronan T
authors.initials: RT
authors.lastname: Swords
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016503:Drug Delivery Systems; D015195:Drug Design; D015507:Drugs, Investigational / Q000494:pharmacology; D006801:Humans; D000075687:NEDD8 Protein; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D044764:Ubiquitin-Activating Enzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D014452:Ubiquitins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014452:Ubiquitins; D044764:Ubiquitin-Activating Enzymes