Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
0numbers the graph read from it
0cells of the map it votes in
4citing 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
15 authors.
Jack Freeland *Department of Molecular and Medical Pharmacology, Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, California.ORCID 0000-0002-8547-1869
Maria Muñoz *Division of Hematology/Oncology, Department of Internal Medicine, University of California, Davis, Sacramento, California.ORCID 0009-0008-5251-3947
Edmond O'DonnellDepartment of Orthopaedic Surgery, University of California, Davis, Sacramento, California.ORCID 0000-0001-9110-9981
Justin LangermanDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, California.ORCID 0009-0003-8376-614X
Morgan DarrowDepartment of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, California.ORCID 0009-0000-8736-8948
Jessica BergonioDivision of Hematology/Oncology, Department of Internal Medicine, University of California, Davis, Sacramento, California.ORCID 0009-0003-2863-5171
Julissa Suarez-NavarroDivision of Hematology/Oncology, Department of Internal Medicine, University of California, Davis, Sacramento, California.ORCID 0000-0002-6484-7433
Steven ThorpeDepartment of Orthopaedic Surgery, University of California, Davis, Sacramento, California.ORCID 0000-0003-3127-4912
Robert CanterDivision of Surgical Oncology, Department of Surgery, University of California, Davis, Sacramento, California.ORCID 0000-0002-3331-5418
Robert Lor RandallDepartment of Orthopaedic Surgery, University of California, Davis, Sacramento, California.ORCID 0000-0002-3660-774X
Kathrin PlathDepartment of Biological Chemistry, University of California, Los Angeles, Los Angeles, California.ORCID 0000-0001-7796-3372
Kermit L CarrawayDepartment of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, California.ORCID 0000-0003-0664-9591
Owen N WitteDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, California.ORCID 0000-0003-4461-4533
Thomas G GraeberDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California.ORCID 0000-0001-8574-9181
Janai R Carr-AscherDivision of Hematology/Oncology, Department of Internal Medicine, University of California, Davis, Sacramento, California.ORCID 0000-0002-2074-4643
Funding
Staff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9M
UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REITER, ROBERT E · 2002 to 2023
$42.6M
Roles of sumoylation and alternative polyadenylation in cellular reprogrammingP01GM099134 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZARET, KENNETH · 2011 to 2021
$20.3M
UC Davis Paul Calabresi K12 Clinical Oncology Research Career Development ProgramK12CA138464 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI BIRKELAND, ANDREW CHARLES, LARA, PRIMO N. · 2011 to 2025
$11.4M
Research Training in Cell and Molecular BiologyT32GM145388 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jorge Torres · 2022 to 2026
$5.2M
Initiative for Maximizing Student Development at the University of California, Davis.T32GM135741 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ALDRIN V. GOMES, Manuel F Navedo · 2020 to 2026
$3.2M
Targeting Genomic Instability in Lethal Neuroendocrine Prostate CancerR01CA222877 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GRAEBER, THOMAS G, WITTE, OWEN N. · 2018 to 2022
$2.6M
MUSCLE: MUsculoSkeletal Clinical Learning Experience Transdisciplinary Musculoskeletal Research Training ProgramT32AR079099 · NIAMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI J. Kent Leach, Robert L. Randall · 2022 to 2026
$844k
Alan B. Slifka FoundationBurroughs Wellcome Fund (BWF)Doris Duke Charitable Foundation (DDCF)Howard Hughes Medical Institute (HHMI)National Cancer Institute (NCI) 5K12-CA138464National Cancer Institute (NCI) RO1CA222877National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) T32AR079099National Institutes of Health (NIH) GM099134National Institutes of Health (NIH) T32GM135741National Institutes of Health (NIH) T32GM145388NCI NIH HHS K12 CA138464NCI NIH HHS P30 CA093373NCI NIH HHS P50 CA092131NCI NIH HHS R01 CA222877NIAMS NIH HHS T32 AR079099NIGMS NIH HHS P01 GM099134NIGMS NIH HHS T32 GM135741NIGMS NIH HHS T32 GM145388W. M. Keck Foundation (WMKF)
6 · The paper itself
Abstract
purposeHigh-grade complex karyotype sarcomas are a heterogeneous group of tumors with a uniformly poor prognosis. Within complex karyotype sarcomas, there are innumerable genetic changes but identifying those that are clinically relevant has been challenging. EXPERIMENTAL
designTo address this, we utilized a pooled genetic screening approach, informed by The Cancer Genome Atlas (TCGA) data, to identify key drivers and modifiers of sarcoma development that were validated in vivo.
resultsYAP1 and wild-type KRAS were validated as drivers and transformed human mesenchymal stem cells into two distinct sarcoma subtypes, undifferentiated pleomorphic sarcoma and myxofibrosarcoma, respectively. A subset of tumors driven by CDK4 and PIK3CA reflected leiomyosarcoma and osteosarcoma demonstrating the plasticity of this approach and the potential to investigate sarcoma subtype heterogeneity. All generated tumors histologically reflected human sarcomas and had increased aneuploidy as compared to simple karyotype sarcomas. Comparing differential gene expression of TCGA samples to model data identified increased oxidative phosphorylation signaling in YAP1 tumors. Treatment of a panel of soft tissue sarcomas with a combination of YAP1 and oxidative phosphorylation inhibitors led to significantly decreased viability.
conclusionsTranscriptional co-analysis of TCGA patient samples to YAP1 and KRAS model tumors supports that these sarcoma subtypes lie along a spectrum of disease and adds guidance for further transcriptome-based refinement of sarcoma subtyping. This approach can be used to begin to understand pathways and mechanisms driving human sarcoma development, the relationship between sarcoma subtypes, and to identify and validate new therapeutic vulnerabilities for this aggressive and heterogeneous disease.
Indexed as
SarcomaTranscription FactorsYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingAnimalsCell Line, TumorGene Expression Regulation, NeoplasticGenetic TestingHumansMiceProto-Oncogene Proteins p21(ras)Xenograft Model Antitumor AssaysAdaptor Proteins, Signal TransducingKRAS protein, humanProto-Oncogene Proteins p21(ras)Transcription FactorsYAP1 protein, humanYAP-Signaling Proteins
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.
Genetic Screen in a Preclinical Model of Sarcoma Development Defines Drivers and Therapeutic Vulnerabilities. · full record | OpenQuestion