VCP/p97/Cdc48, A Linking of Protein Homeostasis and Cancer Therapy

Curr Mol Med. 2017;17(9):608-618. doi: 10.2174/1566524018666180308111238.

Abstract

VCP/p97/Cdc48, a member of the ATPases associated with diverse cellular activities (AAA) family, is necessary for the endoplasmic-reticulum-associated protein degradation (ERAD) pathway to maintain protein homeostasis. Overwhelming proteotoxic stress drove cancer cells to enhance VCP/p97/Cdc48-associated ERAD to maintain protein homeostasis for survival, demonstrating that VCP/p97/Cdc48 expression was positively correlated with cancer prognosis. More studies revealed that targeting VCP/p97/Cdc48 could be a potential target in cancer therapy. CB-5083, a novel inhibitor of VCP/p97/Cdc48, is in clinical trials as the first VCP/p97/Cdc48- inhibiting drug for cancer therapy. Here, we discuss the relationship between VCP/p97/Cdc48, ERAD, protein homeostasis and cancer therapy.

Keywords: CB-5083; ER stress; ERAD; VCP/p97/Cdc48; cancer therapy; protein homeostasis..

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors*
  • Adenosine Triphosphatases / metabolism
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Enzyme Inhibitors / therapeutic use*
  • Homeostasis
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Nuclear Proteins / antagonists & inhibitors*
  • Nuclear Proteins / metabolism
  • Valosin Containing Protein / antagonists & inhibitors*
  • Valosin Containing Protein / metabolism

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Nuclear Proteins
  • Adenosine Triphosphatases
  • p97 ATPase
  • Valosin Containing Protein