Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
26 authors.
Daniel J MerkDepartment of Neurology and Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0003-2935-6919
Foteini TsiamiDepartment of Neurology and Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0009-0001-6070-0434
Sophie HirschDepartment of Neurology and Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.
Bianca WalterDepartment of Neurology and Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0001-9734-4843
Lara A HaeusserDepartment of Neurology and Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0002-3288-4280
Jens D MaileDepartment of Neurology and Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.
Aaron StahlNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, 72770, Germany.ORCID 0000-0003-3616-9564
Mohamed A JarbouiInstitute for Ophtalmic Research, Department for Ophtalmology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0002-5203-235X
Anna Lechado-TerradasLaboratory of Functional Neurogenetics, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, 72076, Germany.ORCID 0000-0003-2650-965X
Franziska KloseInstitute for Ophtalmic Research, Department for Ophtalmology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.
Sepideh BabaeiInternal Medicine I, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0002-5957-6907
Jakob AdmardInstitute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0003-0466-582X
Nicolas CasadeiInstitute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0003-2209-0580
Cristiana RoggiaInstitute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.
Michael SpohnResearch Institute Children's Cancer Center, Hamburg, 20251, Germany.
Jens SchittenhelmInstitute of Neuropathology, Department of Pathology and Neuropathology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0002-9168-6209
Stephan SingerInstitute of General and Molecular Pathology, Department of Pathology and Neuropathology, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.
Ulrich SchüllerResearch Institute Children's Cancer Center, Hamburg, 20251, Germany.ORCID 0000-0002-8731-1121
Federica PiccioniGenetic Perturbation Platform, Broad Institute of MIT and Harvard, MA, Cambridge, 02142, USA.ORCID 0000-0003-1210-3210
Nicole S PerskyGenetic Perturbation Platform, Broad Institute of MIT and Harvard, MA, Cambridge, 02142, USA.ORCID 0000-0002-9948-2761
Manfred ClaassenInternal Medicine I, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0002-4583-9083
Marcos TatagibaDepartment of Neurosurgery, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany.ORCID 0000-0002-1627-9937
Philipp J KahleLaboratory of Functional Neurogenetics, Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, 72076, Germany.ORCID 0000-0002-8587-1731
David E RootGenetic Perturbation Platform, Broad Institute of MIT and Harvard, MA, Cambridge, 02142, USA.ORCID 0000-0001-5122-861X
Markus TemplinNMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, 72770, Germany.ORCID 0000-0002-6569-6489
Ghazaleh TabatabaiDepartment of Neurology and Interdisciplinary Neuro-Oncology, Hertie Institute for Clinical Brain Research, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, 72076, Germany. ghazaleh.tabatabai@uni-tuebingen.de.ORCID 0000-0002-3542-8782
backgroundAtypical teratoid rhabdoid tumors (ATRT) are incurable high-grade pediatric brain tumors. Despite intensive research efforts, the prognosis for ATRT patients under currently established treatment protocols is poor. While novel therapeutic strategies are urgently needed, the generation of molecular-driven treatment concepts is a challenge mainly due to the absence of actionable genetic alterations.
resultsWe here use a functional genomics approach to identify genetic dependencies in ATRT, validate selected hits using a functionally instructed small molecule drug library, and observe preferential activity in ATRT cells without subgroup-specific selectivity. CDK4/6 inhibitors are among the most potent drugs and display anti-tumor efficacy due to mutual exclusive dependency on CDK4 or CDK6. Chemogenetic interactor screens reveal a broad spectrum of G1 phase cell cycle regulators that differentially enable cell cycle progression and modulate response to CDK4/6 inhibition in ATRT cells. In this regard, we find that the ubiquitin ligase substrate receptor AMBRA1 acts as a context-specific inhibitor of cell cycle progression by regulating key components of mitosis including aurora kinases.
conclusionsOur data provide a comprehensive resource of genetic and chemical dependencies in ATRTs, which will inform further preclinical evaluation of novel targeted therapies for this tumor entity. Furthermore, this study reveals a unique mechanism of cell cycle inhibition as the basis for tumor suppressive functions of AMBRA1.
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.
Functional screening reveals genetic dependencies and diverging cell cycle control in atypical teratoid rhabdoid tumors. · full record | OpenQuestion