Therapeutic synergy is also achieved by targeting p66Shc interaction partners; in p53‐wildtype cancers, MDM2 antagonists like Nutlin‐3 increase p53 to induce apoptosis [155], while kinase inhibitors such as EGFR or Akt inhibitors prevent resistance by leveraging p66Shc suppression in the RAS/MAPK and PI3K pathways. The gene discussed is TP53; the disease is cancer.