Valosin-Containing Protein (VCP)/p97: A Prognostic Biomarker and Therapeutic Target in Cancer

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Valosin-containing protein (VCP)/p97 is an AAA+ ATPase molecular chaperone.
• It plays a role in endoplasmic reticulum-associated protein degradation (ERAD).
• VCP/p97 interacts with various cofactors, influencing cancer cell survival and aggressiveness.

Purpose of the Study:

• To review the multifaceted role of VCP/p97 in diverse cancer types.
• To summarize advancements in developing VCP/p97 small-molecule inhibitors for cancer therapy.
• To highlight challenges posed by VCP mutations in therapeutic resistance.

Main Methods:

• Literature review of VCP/p97's function in cancer.
• Analysis of VCP/p97 overexpression data in various malignancies.
• Survey of current small-molecule inhibitor research targeting VCP/p97.
• Examination of VCP mutation-associated resistance mechanisms.

Main Results:

• VCP/p97 is overexpressed across numerous cancer types.
• It is implicated as a potential cancer biomarker and therapeutic target.
• Small-molecule inhibitors targeting VCP/p97 show therapeutic promise.
• Cancer-specific VCP mutations can confer resistance to these inhibitors.

Conclusions:

• VCP/p97 is a significant factor in cancer progression and a viable therapeutic target.
• Targeting VCP/p97 offers a promising avenue for cancer treatment.
• Addressing VCP mutations is critical for overcoming therapeutic resistance and improving patient outcomes.