ArticleNature communications2019
CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary.
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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 81 papers, 1 of them a synthesis that pooled it.
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81citing papers in PubMed, 1 pooled it
5.4field-weighted citation impact, top 3% of its field
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Clinical characteristics and status of treatment of small-cell carcinoma of the ovary, hypercalcemic type in the Chinese population: a meta-analysis.Journal of gynecologic oncology · 2024Pooled it
- 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
- Bibliometric analysis and knowledge mapping of thoracic SMARCA4-deficient undifferentiated tumor.Discover oncology · 2026Article
- SMARCA4 loss reprograms p300 chromatin occupancy to subvert p53-mediated transcriptional repression in ovarian small cell carcinoma.Nature communications · 2026Article
- SMARCA4 mutations drive metastatic progression and predict poor survival in breast cancer based on a real-world cohort study.Discover oncology · 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
- Advanced non-small cell lung cancer with SMARCA4 deficiency: a case report.Frontiers in oncology · 2026Article
- CDK4/6 inhibition with dual immunotherapy in chemorefractory SMARCA4-deficient undifferentiated tumor: a case report.Frontiers in immunology · 2026Article
- Clinical characteristics and prognostic analysis of 22 cases of SMARCA4-deficient thoracic tumors: a retrospective observational study.Journal of thoracic disease · 2025Article
- Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation.Molecular and cellular biochemistry · 2025Review
- Loss of SMARCA4 Leads to Intron Retention and Generation of Tumor-Associated Antigens in Small Cell Carcinoma of the Ovary, Hypercalcemic Type.Cancer research · 2025Article
- Successful treatment with sintilimab for SMARCA4-deficient non-small cell lung carcinoma: two case reports.Discover oncology · 2025Article
- Thoracic SMARCA4-deficient undifferentiated tumor: diagnostic characteristics, molecular insights, and treatment approaches.The oncologist · 2025Article
- Review
- Review
- Single-cell RNA sequencing reveals the intra-tumoral heterogeneity and immune microenvironment of small cell carcinoma of the ovary, hypercalcemic type.Journal of ovarian research · 2025Article
- SMARCA4-deficient primary bone sarcoma with "teratoid" features in a rhabdoid tumor predisposition syndrome patient.Virchows Archiv : an international journal of pathology · 2025Article
- Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer.Science advances · 2025Article
- Super-enhancers and efficacy of triptolide in small cell carcinoma of the ovary hypercalcemic type.iScience · 2025Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
36 authors at 14 institutions in 6 countries.
Yibo XueDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.ORCID http://orcid.org/0000-0003-4252-4446
Brian MeehanDepartment of Pediatrics, McGill University, Montreal, QC, H4A 3J1, Canada.
Elizabeth MacdonaldCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1Y 4E9, Canada.
Sriram VennetiPathology and Neuropathology, University of Michigan Medical School, Ann Arbor, MI, 48109-0605, USA.
Xue Qing D WangDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Leora WitkowskiDepartment of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada.
Petar JelinicGynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, 10016, USA.ORCID http://orcid.org/0000-0002-7361-5239
Tim KongDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Daniel MartinezChildren's Hospital of Philadelphia Research Institute, Philadelphia, PA, 19104, USA.
Geneviève MorinDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Michelle FirlitGynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, 10016, USA.
Atefeh AbediniCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1Y 4E9, Canada.
Radia M JohnsonDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Regina CencicDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Jay PatibandlaGynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, 10016, USA.
Hongbo ChenSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sat University, 510275, Guangzhou, China.
Andreas I PapadakisDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Aurelie AugusteDepartment of Cancer Medicine, Gustave Roussy, INSERM U981, 94800, Villejuif, France.
Iris de RinkGenomics Core Facility, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
Ron M KerkhovenGenomics Core Facility, The Netherlands Cancer Institute, 1066 CX, Amsterdam, The Netherlands.
Nicholas BertosDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Walter H GotliebDivision of Gynecologic Oncology, Segal Cancer Center, Jewish General Hospital, McGill University, Montreal, QC, H3T 1E2, Canada.
Blaise A ClarkeDepartment of Laboratory Medicine and Pathobiology, University of Toronto, University Health Network, Toronto, ON, M5G 2C4, Canada.
Alexandra LearyDepartment of Cancer Medicine, Gustave Roussy, INSERM U981, 94800, Villejuif, France.
Michael WitcherDepartment of Oncology, McGill University, Montreal, QC, H3T 1E2, Canada.
Marie-Christine GuiotDepartment of Pathology, Montreal Neurological Hospital/Institute, McGill University Health Centre, Montreal, QC, H3A 2B4, Canada.
Jerry PelletierDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Josée DostieDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Morag ParkDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada.
Alexander R JudkinsDepartment of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90027, USA.
Ralf HassBiochemistry and Tumor Biology Laboratory, Department of Gynecology and Obstetrics, Medical University Hannover, 30625, Hannover, Germany.ORCID http://orcid.org/0000-0002-2481-7547
Douglas A LevineGynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center, New York, NY, 10016, USA.ORCID http://orcid.org/0000-0003-1038-8232
Janusz RakDepartment of Pediatrics, McGill University, Montreal, QC, H4A 3J1, Canada.
Barbara VanderhydenCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1Y 4E9, Canada.
William D FoulkesDepartment of Human Genetics, McGill University, Montreal, QC, H3A 0C7, Canada. william.foulkes@mcgill.ca.ORCID http://orcid.org/0000-0001-7427-4651
Sidong HuangDepartment of Biochemistry, McGill University, Montreal, QC, H3G 1Y6, Canada. sidong.huang@mcgill.ca.ORCID http://orcid.org/0000-0002-2838-4726
McGill University Health Centre · CAGynecologic Oncology Group · USUniversity of Ottawa · CAInserm · FRJewish General Hospital · CAMcGill University · CAMontreal Children's Hospital · CAThe Netherlands Cancer Institute · NLChildren's Hospital of Philadelphia · USMedizinische Hochschule Hannover · DESun Yat-sen University · CNUniversity Health Network · CAUniversity of Michigan · USUniversity of Southern California · US
Funding
Canadian HIV Trials Network, Canadian Institutes of Health Research (Réseau canadien pour les essais VIH des IRSC) PJT-156233DOD | Congressionally Directed Medical Research Programs (CDMRP) W81XWH-15-1-0497Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) MOP-130540
Abstract
Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16
Indexed as
AminopyridinesAnimalsBenzimidazolesCarcinoma, Small CellCell Line, TumorCell SurvivalChromatin ImmunoprecipitationCyclin D1DNA HelicasesFemaleHumansHypercalcemiaMiceMice, SCIDNuclear ProteinsOvarian NeoplasmsabemaciclibAminopyridinesBenzimidazolesCyclin D1DNA HelicasesNuclear ProteinspalbociclibPiperazinesProtein Kinase InhibitorsPurinesPyridinesribociclibRNA, Small InterferingSMARCA4 protein, humanTranscription Factors
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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.