ArticleProceedings of the National Academy of Sciences of the United States of America2014
Functional epigenetics approach identifies BRM/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 244 papers.
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Who cites it
244 citing papers in PubMed, 409 citations in OpenAlex.
- A DoE-Dual centrifugation-driven screening platform for liposomal incorporation of poorly soluble APIs: Application to the PROTAC ACBI2.International journal of pharmaceutics: X · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Delineating SWI/SNF gene and subtype expression in cancer.Epigenetics & chromatin · 2026Article
- 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
- Discovery of SMD-6346: A Potent, Selective, and Orally Active SMARCA2 Degrader for Targeting SMARCA4-Deficient Human Cancers.Journal of medicinal chemistry · 2026Article
- Characterization ofBiomolecules · 2026Article
- Targeting the CHD3 chromatin remodeler exploits a synthetic lethal vulnerability in dual SMARCA4/SMARCA2-deficient cancers via derepression of PARD3B.NPJ precision oncology · 2026Article
- Two distinct SWI/SNF complexes direct chromatin-linked transcriptional programs in Toxoplasma.Nature communications · 2026Article
- Synthetic lethality in cancer: mechanism exploration and therapeutic applications.Cell communication and signaling : CCS · 2026Review
- Article
- Analysis of SWI Complex Subunits in 69 Cases of TTF-1 Negative Non-Small Cell Lung Carcinoma.Diagnostic cytopathology · 2026Article
- mSWI/SNF complex inhibition sensitizes KRAS-mutant lung cancers to targeted therapies via epithelial-mesenchymal subversion.bioRxiv : the preprint server for biology · 2026Article
- Targeted regeneration of post-radiation epithelium without promoting cancer recurrence.Research square · 2026Article
- SWI/SNF Chromatin Remodelling Complex in Hepatic Physiology: Mechanistic Insights Into Development, Homeostasis and Pathogenesis.Journal of cellular and molecular medicine · 2026Review
- Case Report: Thoracic SMARCA4-deficient undifferentiated tumor with extraocular muscle metastasis: a rare case hidden in diplopia.Frontiers in medicine · 2026Article
- Expression Profiling of SWI/SNF Complex Subunits in Triple-Negative Breast Cancer Using Tissue Microarray and Immunohistochemistry.Breast cancer (Dove Medical Press) · 2026Article
- Catalytic-independent roles of chromatin modifiers in mammalian development and the implications for treating human disease.Biochemical Society transactions · 2025Review
- Rational design of potent small-molecule SMARCA2/A4 degraders acting via the recruitment of FBXO22.Nature communications · 2025Article
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
184 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Defects in epigenetic regulation play a fundamental role in the development of cancer, and epigenetic regulators have recently emerged as promising therapeutic candidates. We therefore set out to systematically interrogate epigenetic cancer dependencies by screening an epigenome-focused deep-coverage design shRNA (DECODER) library across 58 cancer cell lines. This screen identified BRM/SMARCA2, a DNA-dependent ATPase of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex, as being essential for the growth of tumor cells that harbor loss of function mutations in BRG1/SMARCA4. Depletion of BRM in BRG1-deficient cancer cells leads to a cell cycle arrest, induction of senescence, and increased levels of global H3K9me3. We further demonstrate the selective dependency of BRG1-mutant tumors on BRM in vivo. Genetic alterations of the mSWI/SNF chromatin remodeling complexes are the most frequent among chromatin regulators in cancers, with BRG1/SMARCA4 mutations occurring in ∼10-15% of lung adenocarcinomas. Our findings position BRM as an attractive therapeutic target for BRG1 mutated cancers. Because BRG1 and BRM function as mutually exclusive catalytic subunits of the mSWI/SNF complex, we propose that such synthetic lethality may be explained by paralog insufficiency, in which loss of one family member unveils critical dependence on paralogous subunits. This concept of "cancer-selective paralog dependency" may provide a more general strategy for targeting other tumor suppressor lesions/complexes with paralogous subunits.
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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.