Figure 2.

Strategies for targeting mutant p53 and wild-type p53 in cancer cells. Pharmacological approaches for targeting wild-type and mutant p53 in cancer cells are focused on small molecules (upper panel). Small molecules targeting wild-type p53 activation via binding to p53 (such as RITA), inhibition of MDM2/X (such as an MDM2 inhibitor nutlin-3 and the dual inhibitor ALRN6924), post-translational modifications (such as tenovin). Small molecules target mutant p53 via restoration of p53 function (such as PRIMA-1), degradation of mutant p53 via activation of MDM2 (such as 17AAG and NSC59984) or interruption of mutant p53-p73 interaction (such as RETRA). Activation of p73 upregulates p53 target gene expression and induces cell death. Biotherapeutic approaches are based on gene transfection and genomic modifications (bottom panel). p53 is transfected into cancer cells with an adenovirus to replace mutant p53, and upregulates p53 signaling (such as rADp53). Genomic editing is used to restore wild-type p53 or delete mutant p53 in cancer cells by genome editing approaches (such as CRISPR). A bispecific antibody with mutant p53-specific peptide and ALH ligands promotes T cells to recognize and kill p53-mutant tumor cells in cancer immunotherapy.