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Article

MDM2 antagonists overcome intrinsic resistance to CDK4/6 inhibition by inducing p21

14 Aug 2019

Abstract excerpt

Intrinsic resistance of unknown mechanism impedes the clinical utility of inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) in malignancies other than breast cancer. Here, we used melanoma patient-derived xenografts (PDXs) to study the mechanisms for CDK4/6i resistance in preclinical settings. We observed that melanoma PDXs resistant to CDK4/6i frequently displayed activation of the phosphatidylinositol...

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PMID: 31413145
DOI: 10.1126/scitranslmed.aav7171

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