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MDM2-TP53 Crossregulation: An Underestimated Target to Promote Loss of TP53 Function and Cell Survival
1Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska (CCK) R8:04, Stockholm SE-171 76, Sweden; Université Pierre et Marie Curie, Paris, France; INSERM U1138, Centre de Recherche des Cordeliers, Paris, France; Equipe11 labellisée Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
Abstract:
Half of human cancers bear inactivating mutations of the tumor suppressor gene TP53, but the other half do not. In a recent issue of Cancer Cell, Dhar et al. and Zhu et al. reported that, in liver cancer and medulloblastoma, MDM2 is constitutively activated, causing a loss of TP53 function that does not require TP53 mutation. On theoretical grounds, such cancer would be amenable to treatment with MDM2 inhibitors.
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