ArticleJCO precision oncology2024
Combination of MDM2 and Targeted Kinase Inhibitors Results in Prolonged Tumor Control in Lung Adenocarcinomas With Oncogenic Tyrosine Kinase Drivers and
Article in JCO precision oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The trial behind it
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Who cites it
5 citing papers in PubMed.
- Milademetan in Advanced Solid Tumors with MDM2 Amplification and Wild-type TP53: Preclinical and Phase II Clinical Trial Results.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- MDM2 in Tumor Biology and Cancer Therapy: A Review of Current Clinical Trials.International journal of molecular sciences · 2025Review
- Dual-targeted N-PMIMaterials today. Bio · 2025Article
- Identifying the genomic landscape of EGFR-mutant lung cancers with central nervous system metastases.Annals of oncology : official journal of the European Society for Medical Oncology · 2025Article
- ZNF146 accelerates lung adenocarcinoma progression through MDM2/p53 and PHGDH/ferroptosis.Cell & bioscience · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
purposeMDM2, a negative regulator of the TP53 tumor suppressor, is oncogenic when amplified.
methodsWe evaluated the combination of MDM2 and RTK inhibition in patient-derived models of LUAD.
resultsIn a RET-fusion LUAD patient-derived model with MDM2amp, MDM2 inhibition with either milademetan or AMG232 combined with selpercatinib resulted in long-term in vivo tumor control markedly superior to either agent alone. Similarly, in an EGFR-mutated model with MDM2amp, combining either milademetan or AMG232 with osimertinib resulted in long-term in vivo tumor control, which was strikingly superior to either agent alone.
conclusionThese preclinical in vivo data provide a rationale for further clinical development of this combinatorial targeted therapy approach.
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Registered trials
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