Evidence map›Paper›PMID 31461650›Full record

ArticleCell reports2019

Small-Molecule and CRISPR Screening Converge to Reveal Receptor Tyrosine Kinase Dependencies in Pediatric Rhabdoid Tumors.

Elaine M Oberlick, Matthew G Rees, Brinton Seashore-Ludlow, Francisca Vazquez, Geoffrey M Nelson, Neekesh V Dharia, Barbara A Weir, Aviad Tsherniak, Mahmoud Ghandi, John M Krill-Burger and 18 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% of its field
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.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.

  1. Pooled it
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  4. Article
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  7. Article
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  10. Chromatin remodellers as therapeutic targets.Nature reviews. Drug discovery · 2024
    Review
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  12. Article
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  15. Targeting SHP2 phosphatase in hematological malignancies.Expert opinion on therapeutic targets · 2022
    Review
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4 · The record

Corrections and comments

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

28 authors at 4 institutions in 2 countries.

Elaine M OberlickDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115, USA; Broad Institute, Cambridge, MA 02142, USA.
Matthew G ReesBroad Institute, Cambridge, MA 02142, USA. Electronic address: reesm@broadinstitute.org.
Brinton Seashore-LudlowBroad Institute, Cambridge, MA 02142, USA; Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institute, 171 77 Stockholm, Sweden.
Francisca VazquezBroad Institute, Cambridge, MA 02142, USA.
Geoffrey M NelsonDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Neekesh V DhariaDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02215, USA; Boston Children's Hospital, Boston, MA 02115, USA.
Barbara A WeirBroad Institute, Cambridge, MA 02142, USA.
Aviad TsherniakBroad Institute, Cambridge, MA 02142, USA.
Mahmoud GhandiBroad Institute, Cambridge, MA 02142, USA.
John M Krill-BurgerBroad Institute, Cambridge, MA 02142, USA.
Robin M MeyersBroad Institute, Cambridge, MA 02142, USA.
Xiaofeng WangDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Phil MontgomeryBroad Institute, Cambridge, MA 02142, USA.
David E RootBroad Institute, Cambridge, MA 02142, USA.
Jake M BieberBroad Institute, Cambridge, MA 02142, USA.
Sandi RadkoComprehensive Cancer Center and Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Jaime H CheahBroad Institute, Cambridge, MA 02142, USA.
C Suk-Yee HonBroad Institute, Cambridge, MA 02142, USA.
Alykhan F ShamjiBroad Institute, Cambridge, MA 02142, USA.
Paul A ClemonsBroad Institute, Cambridge, MA 02142, USA.
Peter J ParkDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Harvard Ludwig Center, Harvard Medical School, Boston, MA 02115, USA.
Michael A DyerDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Todd R GolubBroad Institute, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02215, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Kimberly StegmaierDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute, Cambridge, MA 02142, USA; Boston Children's Hospital, Boston, MA 02115, USA.
William C HahnBroad Institute, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Elizabeth A StewartDepartment of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Stuart L SchreiberBroad Institute, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Charles W M RobertsComprehensive Cancer Center and Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: charles.roberts@stjude.org.
Broad Institute · USHarvard University · USSt. Jude Children's Research Hospital · USDana-Farber Cancer Institute · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
The Dana-Farber Cancer Institute Cancer Target Discovery and Development CenterU01CA176058 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2013 to 2021
$7.8M
THE FUNCTION OF SNF5 (SMARCB1), AN EPIGENETIC TUMOR SUPPRESSORR01CA113794 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 2005 to 2026
$7.8M
Targeting vulnerabilities of therapy-resistant cancer cell states with small moleculesU01CA217848 · NCI · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2017 to 2021
$5.8M
Role of the SWI/SNF complex in tumor suppressionR01CA172152 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 2013 to 2026
$5.1M
Cancer dependencies associated with genomic alterations and targeted by small molU01CA176152 · NCI · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2013 to 2016
$4.4M
The Role of SWI/SNF Alternative Splicing in CancerF31CA183558 · NCI · HARVARD MEDICAL SCHOOL · PI OBERLICK, ELAINE MARIE · 2013 to 2015
$99k
Howard Hughes Medical InstituteNCI NIH HHS F31 CA183558NCI NIH HHS P30 CA021765NCI NIH HHS R01 CA113794NCI NIH HHS R01 CA172152NCI NIH HHS U01 CA176058NCI NIH HHS U01 CA176152NCI NIH HHS U01 CA217848
6 · The paper itself

Abstract

Cancer is often seen as a disease of mutations and chromosomal abnormalities. However, some cancers, including pediatric rhabdoid tumors (RTs), lack recurrent alterations targetable by current drugs and need alternative, informed therapeutic options. To nominate potential targets, we performed a high-throughput small-molecule screen complemented by a genome-scale CRISPR-Cas9 gene-knockout screen in a large number of RT and control cell lines. These approaches converged to reveal several receptor tyrosine kinases (RTKs) as therapeutic targets, with RTK inhibition effective in suppressing RT cell growth in vitro and against a xenograft model in vivo. RT cell lines highly express and activate (phosphorylate) different RTKs, creating dependency without mutation or amplification. Downstream of RTK signaling, we identified PTPN11, encoding the pro-growth signaling protein SHP2, as a shared dependency across all RT cell lines. This study demonstrates that large-scale perturbational screening can uncover vulnerabilities in cancers with "quiet" genomes.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCRISPR-Cas SystemsFemaleHEK293 CellsHumansMiceMice, NudeMutationProtein Kinase InhibitorsProtein Tyrosine Phosphatase, Non-Receptor Type 11Rhabdoid TumorSmall Molecule LibrariesAntineoplastic AgentsProtein Kinase InhibitorsProtein Tyrosine Phosphatase, Non-Receptor Type 11PTPN11 protein, humanSmall Molecule Librariesgenome-wide CRISPR screeninghigh-throughput drug screeningPTPN11receptor tyrosine kinaserhabdoid tumorsSMARCB1

Identifiers

PMID31461650
PMCPMC7319190
OpenAlexW2971104097

What OpenQuestion holds

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Registered trials

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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.