ArticleNature communications2021
SMARCA4 deficient tumours are vulnerable to KDM6A/UTX and KDM6B/JMJD3 blockade.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 58 citations in OpenAlex.
- A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: durable responses and delayed pseudoprogression in small cell carcinoma of the ovary, hypercalcemic type cohort.Cancer communications (London, England) · 2025Trial
- Interpreting human genetic variation at atomic resolution.Nature genetics · 2026Review
- Histone Methylation and Chromatin Remodeling in Non-Small Cell Lung Cancer: Mechanisms of Oncogenesis and Emerging Therapeutic Strategies.Biomedicines · 2026Review
- The Removal of H3K27me3 PromotedCells · 2026Article
- UTY (KDM6C) in Cancer: Epigenetic Regulation, Tumour Suppressor Functions, and Clinical Implications.Epigenomes · 2026Review
- Embryonic stem cell factors DPPA2/4 amplify active H3K4me3-H2AK119ub chromatin domains in non-small cell lung cancer.Genes & development · 2026Article
- Analysis of SWI Complex Subunits in 69 Cases of TTF-1 Negative Non-Small Cell Lung Carcinoma.Diagnostic cytopathology · 2026Article
- [Clinicopathological, Genomic Characteristics and Prognostic Analysis in 18 Cases of SMARCA4-deficient or SMARCA4-mutated Pulmonary Tumors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- SMARCA4/2 loss reduces BCL-xL expression and confers a druggable MCL1 dependency in cancer.NPJ precision oncology · 2026Article
- The Role of Histone Methylation in Heart Failure: Epigenetic Mechanisms and Therapeutic Perspectives.Drug design, development and therapy · 2026Review
- Clinical characteristics and prognostic analysis of 22 cases of SMARCA4-deficient thoracic tumors: a retrospective observational study.Journal of thoracic disease · 2025Article
- KDM6B inhibition enhances chemotherapeutic response in small cell lung cancer via epigenetic regulation of apoptosis and ferroptosis.Cell & bioscience · 2025Article
- KDM6A phosphorylation suppresses PER2 to confer a glycolytic vulnerability in HNSCC.Cell death & disease · 2025Article
- Activation of sphingosine-1-phosphate receptor 2 (S1PR2) upregulates dihydropyrimidine dehydrogenase (DPD) expression in colon cancer cells.Journal of advanced research · 2025Article
- Epigenetic synthetic lethality as a cancer therapeutic strategy: synergy of experimental and computational approaches.Epigenomics · 2025Review
- The role of SMARCA4 in lung cancer.Scientific reports · 2025Review
- Concurrent SMARCA4-deficient and poorly differentiated adenocarcinomas in separate lung lobes: a case report and literature review.World journal of surgical oncology · 2025Review
- Discovery of Novel, Potent, and Orally Bioavailable SMARCA2 Proteolysis-Targeting Chimeras with Synergistic Antitumor Activity in Combination with Kirsten Rat Sarcoma Viral Oncogene Homologue G12C Inhibitors.Journal of medicinal chemistry · 2025Article
- Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer.Science advances · 2025Article
- Primary gastric SMARCA4-deficient carcinosarcoma and sarcomatoid carcinoma: Two case reports.Frontiers in oncology · 2025Article
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the genetic inactivation of SMARCA4, a core component of the SWI/SNF-complex commonly found in cancer, there are no therapies that effectively target SMARCA4-deficient tumours. Here, we show that, unlike the cells with activated MYC oncogene, cells with SMARCA4 inactivation are refractory to the histone deacetylase inhibitor, SAHA, leading to the aberrant accumulation of H3K27me3. SMARCA4-mutant cells also show an impaired transactivation and significantly reduced levels of the histone demethylases KDM6A/UTX and KDM6B/JMJD3, and a strong dependency on these histone demethylases, so that its inhibition compromises cell viability. Administering the KDM6 inhibitor GSK-J4 to mice orthotopically implanted with SMARCA4-mutant lung cancer cells or primary small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), had strong anti-tumour effects. In this work we highlight the vulnerability of KDM6 inhibitors as a characteristic that could be exploited for treating SMARCA4-mutant cancer patients.
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