Directly inhibiting the enzymatic activity of USP7 with or without binding to the catalytic domain by small-molecule inhibitors may cause the degradation of all the substrates of USP7, regardless of tumor suppressors (e.g., p53 and PTEN) and oncoproteins (e.g., MDM2 and MDMX), which may cause adverse effects in cancer patients. Here, MDM4 is linked to cancer.