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Suggested mechanism of VIP116-mediated potentiation of 177Lu-DOTATATE in neuroblastoma. 177Lu-DOTATATE causes DNA double strand breaks which initiates a slight p53-mediated response. VIP116 is able to enhance the p53 response and induce transcription of downstream targets, leading to increased apoptosis. MYCN, which can be induced or repressed by the therapies via unknown mechanisms, can affect p53 function negatively via MDM2 transcription or blocking p21-mediated cell cycle arrest.
