ArticleCommunications biology2022
GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Sequential use of PI3K/AKT/mTOR pathway inhibitors alpelisib and everolimus in patients with hormone receptor-positive metastatic breast cancer.Breast cancer research : BCR · 2026Observational
- Concurrent genomic assessment of circulating tumour cells and ctDNA to guide therapy in metastatic breast cancer.BMC cancer · 2025Article
- Cytotoxic and proapoptotic effects of alizarin in mice with Ehrlich solid tumor: novel insights into ERα-mediated MDM2/p-Rb/E2F1 signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Integrating large-scale in vitro functional genomic screen and multi-omics data to identify novel breast cancer targets.Breast cancer research and treatment · 2025Article
- In Silico Analysis Reveals MDM2 as a Potential Target of Ursolic Acid for Overcoming Tamoxifen Resistance in Breast Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Genomic and proteomic profiling of GATA3 mutant metastatic hormone receptor-positive breast cancer and impact on clinical outcomes.Breast cancer research and treatment · 2025Article
- Discovery of epigenetically silenced tumour suppressor genes in aggressive breast cancer through a computational approach.NAR cancer · 2025Article
- Perspectives on cancer therapy-synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges.Cell death discovery · 2025Review
- Highlighting recent achievements to advance more effective cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Article
- LncRNA PVT1 links estrogen receptor alpha and the polycomb repressive complex 2 in suppression of pro-apoptotic genes in hormone-responsive breast cancer.Cell death & disease · 2025Article
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
- SpatialSNV: A novel method for identifying and analyzing spatially resolved SNVs in tumor microenvironments.GigaScience · 2025Article
- Targeting MDM2-p53 interaction for breast cancer therapy.Oncology research · 2025Review
- Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios.Genome medicine · 2024Article
- Prevalent landscape of tumor genomic alterations of luminal B1 breast cancers using a comprehensive genomic profiling assay in Taiwan.Breast cancer (Tokyo, Japan) · 2024Article
- Case report: Near-complete response to neratinib-based treatment in HR-positiveFrontiers in oncology · 2024Article
- Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens.Nature communications · 2022Article
- Integrated multi-omics profiling of high-grade estrogen receptor-positive, HER2-negative breast cancer.Molecular oncology · 2022Article
- P53 Suppressor Gene Tissue Microarray-based Protein Expression Analysis in Meningiomas.In vivo (Athens, Greece)Article
Corrections and comments
- Erratum issued
Authors and funding
26 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synthetic lethal interactions, where the simultaneous but not individual inactivation of two genes is lethal to the cell, have been successfully exploited to treat cancer. GATA3 is frequently mutated in estrogen receptor (ER)-positive breast cancers and its deficiency defines a subset of patients with poor response to hormonal therapy and poor prognosis. However, GATA3 is not yet targetable. Here we show that GATA3 and MDM2 are synthetically lethal in ER-positive breast cancer. Depletion and pharmacological inhibition of MDM2 significantly impaired tumor growth in GATA3-deficient models in vitro, in vivo and in patient-derived organoids/xenograft (PDOs/PDX) harboring GATA3 somatic mutations. The synthetic lethality requires p53 and acts via the PI3K/Akt/mTOR pathway. Our results present MDM2 as a therapeutic target in the substantial cohort of ER-positive, GATA3-mutant breast cancer patients. With MDM2 inhibitors widely available, our findings can be rapidly translated into clinical trials to evaluate in-patient efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.