Evidence map›Paper›PMID 29617654›Full record

ArticleCell reports2018

Identification of CDC25 as a Common Therapeutic Target for Triple-Negative Breast Cancer.

Jeff C Liu, Letizia Granieri, Mariusz Shrestha, Dong-Yu Wang, Ioulia Vorobieva, Elizabeth A Rubie, Rob Jones, YoungJun Ju, Giovanna Pellecchia, Zhe Jiang and 7 more

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

Article in Cell reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.9field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
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  9. Article
  10. Strategy of combining CDK4/6 inhibitors with other therapies and mechanisms of resistance.International journal of clinical and experimental pathology · 2024
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. WEE1 Dependency and Pejorative Prognostic Value in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021
    Review
  20. TargetingCancers · 2021
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 3 countries.

Jeff C LiuToronto General Research Institute - University Health Network, 67 College Street, Toronto, ON, Canada M5G 2M1.
Letizia GranieriToronto General Research Institute - University Health Network, 67 College Street, Toronto, ON, Canada M5G 2M1; Department of Agriculture, Food, and Environmental Sciences, University of Perugia, Perugia, Italy.
Mariusz ShresthaToronto General Research Institute - University Health Network, 67 College Street, Toronto, ON, Canada M5G 2M1; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Dong-Yu WangToronto General Research Institute - University Health Network, 67 College Street, Toronto, ON, Canada M5G 2M1.
Ioulia VorobievaToronto General Research Institute - University Health Network, 67 College Street, Toronto, ON, Canada M5G 2M1; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada.
Elizabeth A RubieLunenfeld-Tanenbaum Research Institute, Sinai Health System, 600 University Avenue, Toronto, ON, Canada.
Rob JonesToronto General Research Institute - University Health Network, 67 College Street, Toronto, ON, Canada M5G 2M1.
YoungJun JuToronto General Research Institute - University Health Network, 67 College Street, Toronto, ON, Canada M5G 2M1.
Giovanna PellecchiaThe Donnelly Centre, University of Toronto, Toronto, ON, Canada; The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, ON, Canada.
Zhe JiangToronto General Research Institute - University Health Network, 67 College Street, Toronto, ON, Canada M5G 2M1.
Carlo A PalmeriniDepartment of Agriculture, Food, and Environmental Sciences, University of Perugia, Perugia, Italy.
Yaacov Ben-DavidThe Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, Guizhou 550014, China; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, Guizhou 550025, China.
Sean E EganDepartment of Molecular Genetics, University of Toronto, Toronto, ON, Canada; Program in Cell Biology, The Peter Gilgan Center for Research and Learning, The Hospital for Sick Children, Toronto, ON, Canada.
James R WoodgettLunenfeld-Tanenbaum Research Institute, Sinai Health System, 600 University Avenue, Toronto, ON, Canada.
Gary D BaderThe Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Alessandro DattiDepartment of Agriculture, Food, and Environmental Sciences, University of Perugia, Perugia, Italy; Network Biology Collaborative Centre, SMART Laboratory for High-Throughput Screening Programs, Mount Sinai Hospital, Toronto, ON, Canada.
Eldad ZacksenhausToronto General Research Institute - University Health Network, 67 College Street, Toronto, ON, Canada M5G 2M1; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address: eldad.zacksenhaus@utoronto.ca.
University Health Network · CAUniversity of Toronto · CALunenfeld-Tanenbaum Research Institute · CAUniversity of Perugia · ITGuiyang Medical University · CNHospital for Sick Children · CA

Funding

TR&D 3 - Network Guided Machine LearningP41GM103504 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2012 to 2024
$17.3M
Pathway Commons: Research Resource for Biological PathwaysU41HG006623 · NHGRI · SLOAN-KETTERING INST CAN RESEARCH · PI SANDER, CHRIS · 2012 to 2017
$5.7M
Cytoscape: A Modeling Platform for Biomolecular NetworksR01GM070743 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2004 to 2016
$5.7M
CIHRNHGRI NIH HHS U41 HG006623NIGMS NIH HHS P41 GM103504NIGMS NIH HHS R01 GM070743
6 · The paper itself

Abstract

CDK4/6 inhibitors are effective against cancer cells expressing the tumor suppressor RB1, but not RB1-deficient cells, posing the challenge of how to target RB1 loss. In triple-negative breast cancer (TNBC), RB1 and PTEN are frequently inactivated together with TP53. We performed kinome/phosphatase inhibitor screens on primary mouse Rb/p53-, Pten/p53-, and human RB1/PTEN/TP53-deficient TNBC cell lines and identified CDC25 phosphatase as a common target. Pharmacological or genetic inhibition of CDC25 suppressed growth of RB1-deficient TNBC cells that are resistant to combined CDK4/6 plus CDK2 inhibition. Minimal cooperation was observed in vitro between CDC25 antagonists and CDK1, CDK2, or CDK4/6 inhibitors, but strong synergy with WEE1 inhibition was apparent. In accordance with increased PI3K signaling following long-term CDC25 inhibition, CDC25 and PI3K inhibitors effectively synergized to suppress TNBC growth both in vitro and in xenotransplantation models. These results provide a rationale for the development of CDC25-based therapies for diverse RB1/PTEN/TP53-deficient and -proficient TNBCs.

Indexed as

AnimalsAntineoplastic Agentscdc25 PhosphatasesCell Line, TumorCell ProliferationEnzyme InhibitorsFemaleHumansMiceMice, Inbred NODMice, SCIDPTEN PhosphohydrolaseRetinoblastoma Binding ProteinsTriple Negative Breast NeoplasmsTumor Suppressor Protein p53Antineoplastic Agentscdc25 PhosphatasesEnzyme InhibitorsPTEN PhosphohydrolaseRetinoblastoma Binding ProteinsTumor Suppressor Protein p53basal-like breast cancerCDC25checkpoint controlCHK1PTENRB1therapyTP53triple negative breast cancerWEE1

Identifiers

PMID29617654
PMCPMC9357459
OpenAlexW2795575061

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.