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