TP53 and metastatic melanoma: APG-115 is an MDM2 inhibitor could activate p53 through MDM2-p53 interaction, and its combination with pembrolizumab has been shown good tolerability and preliminary indications of antitumor activity in a clinical trial for patients with metastatic melanoma and advanced-stage solid tumors (NCT03611868).403,405 Besides, the synergistic effects of p53 activation and immunotherapy have also been verified in gene therapy modules, providing promising evidence for further attempts at combined application.615