ArticleNature communications2019
SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in non-small cell lung cancer.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 183 citations in OpenAlex.
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- The role of OLMALINC in small cell lung cancer progression and prognosis.Molecular and cellular biochemistry · 2026Article
- SMARCA4 loss reprograms p300 chromatin occupancy to subvert p53-mediated transcriptional repression in ovarian small cell carcinoma.Nature communications · 2026Article
- CSF1R inhibitors mitigate CDK4/6 inhibitor-induced immunosuppression to increase antitumor immunity in HR+/HER2- breast cancer.Oncogene · 2026Article
- SWI/SNF-Deficient Sinonasal Carcinomas: A Retrospective Case Series of 17 Patients from a Single Institution.Journal of clinical medicine · 2026Article
- A Double-Negative Prostate Cancer Subtype Is Vulnerable to SWI/SNF-Targeting Degrader Molecules.Cancer research · 2026Article
- An update on the role of SMARCA4 deficiency in gynecological neoplasms: how and where.Virchows Archiv : an international journal of pathology · 2026Review
- SMARCA4/2 loss reduces BCL-xL expression and confers a druggable MCL1 dependency in cancer.NPJ precision oncology · 2026Article
- MVGAE: A Multi-View Graph Auto-Encoder Model for Drug Prediction of Non-Small Cell Lung Cancer Based on Synthetic Lethality.Current issues in molecular biology · 2026Article
- Intrathoracic Rhabdoid Tumors Showing Rapid Progress in Patients with a History of Immune-suppressive Therapies for Hematological Diseases.Internal medicine (Tokyo, Japan) · 2026Article
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- Potential of small-molecule targeted drugs in combination with CAR-T cell therapy for hematologic lymphomas.Frontiers in immunology · 2026Review
- CDK4/6 inhibition with dual immunotherapy in chemorefractory SMARCA4-deficient undifferentiated tumor: a case report.Frontiers in immunology · 2026Article
- DDOST mediates cervical cancer cell malignant progression by interacting with SMARCA4.American journal of cancer research · 2026Article
- Immunotherapy plus chemotherapy improves survival in SMARCA4-deficient NSCLC: a real-world cohort study.Frontiers in immunology · 2026Article
- Epigenetic reprogramming as the nexus of cancer stemness and therapy resistance: implications for biomarker discovery.Discover oncology · 2025Review
- Genomic Landscapes of Endometrioid and Mucinous Ovarian Cancers and Morphologically Similar Tumor Types.Cancer research communications · 2025Article
- BRG1 Loss Is Frequent in Lung Cancer and Transforms Lung Epithelial Cells via Transcriptional and Epigenetic Reprograming.Cancers · 2025Article
- A double-negative prostate cancer subtype is vulnerable to SWI/SNF-targeting degrader molecules.bioRxiv : the preprint server for biology · 2025Article
- The role of SMARCA4 in lung cancer.Scientific reports · 2025Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
27 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor suppressor SMARCA4 (BRG1), a key SWI/SNF chromatin remodeling gene, is frequently inactivated in cancers and is not directly druggable. We recently uncovered that SMARCA4 loss in an ovarian cancer subtype causes cyclin D1 deficiency leading to susceptibility to CDK4/6 inhibition. Here, we show that this vulnerability is conserved in non-small cell lung cancer (NSCLC), where SMARCA4 loss also results in reduced cyclin D1 expression and selective sensitivity to CDK4/6 inhibitors. In addition, SMARCA2, another SWI/SNF subunit lost in a subset of NSCLCs, also regulates cyclin D1 and drug response when SMARCA4 is absent. Mechanistically, SMARCA4/2 loss reduces cyclin D1 expression by a combination of restricting CCND1 chromatin accessibility and suppressing c-Jun, a transcription activator of CCND1. Furthermore, SMARCA4 loss is synthetic lethal with CDK4/6 inhibition both in vitro and in vivo, suggesting that FDA-approved CDK4/6 inhibitors could be effective to treat this significant subgroup of NSCLCs.
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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.