Murine Double Minute 2 (MDM2) is an E3 ubiquitin ligase and negative regulator of the tumor suppressor protein p53. Under normal conditions, MDM2 is constitutively spliced to generate a full-length protein and promotes the proteasome-mediated degradation of p53. However, under stress MDM2 undergoes alternative splicing, generating splice variants that are unable to bind and regulate p53. Subsequently, p53 becomes upregulated and activates downstream targets involved in apoptosis and cell cycle arrest. Investigators at Nationwide Children's Hospital have developed a novel splicing corrective treatment to modulate the splicing of p53-modifier MDM2 in cancer.