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In line with this, the clinical development of MDM2 inhibitors currently focuses on strategies that limit selection of TP53-mutant-positive clones, including intermittent schedules, combinations with DNA-damaging chemotherapy, tyrosine kinase inhibitors, or immunotherapy, as well as dual-targeting approaches, i.e., concurrent inhibition of MDM2 and MDM4, which may reduce the risk of escape via MDM4-dependent mechanisms [274,333]
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