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.
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