Evidence map›Paper›PMID 23974104›Full record

ArticleCell cycle (Georgetown, Tex.)2013

High-throughput screen identifies disulfiram as a potential therapeutic for triple-negative breast cancer cells: interaction with IQ motif-containing factors.

Tyler J W Robinson, Melody Pai, Jeff C Liu, Frederick Vizeacoumar, Thomas Sun, Sean E Egan, Alessandro Datti, Jing Huang, Eldad Zacksenhaus

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03323346 (Phase II Open Labeled Trial of Disulfiram With Copper in Metastatic Breast Cancer), which is not on this map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.1field-weighted citation impact, top 14% 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.

NCT03323346 phase2completednot on this mapstarted 2017, after this paper: background citation

Phase II Open Labeled Trial of Disulfiram With Copper in Metastatic Breast Cancer

TypeinterventionalSponsorThe Institute of Molecular and Translational Medicine, Czech RepublicRan2017 to 2025Enrolled9ConditionsBreast Neoplasm Female, Metastatic Breast CancerArmsDisulfiram
3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 51 citations in OpenAlex.

  1. Review
  2. Non-Muscle Myosin II A: Friend or Foe in Cancer?International journal of molecular sciences · 2024
    Review
  3. Review
  4. Article
  5. Stability-based approaches in chemoproteomics.Expert reviews in molecular medicine · 2024
    Review
  6. Review
  7. The Knowns and Unknowns in Protein-Metabolite Interactions.International journal of molecular sciences · 2023
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Ras GTPase-Activating-Like Protein IQGAP1 (IQGAP1) Promotes Breast Cancer Proliferation and Invasion and Correlates with Poor Clinical Outcomes.Medical science monitor : international medical journal of experimental and clinical research · 2018
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

9 authors at 6 institutions in 6 countries.

Tyler J W RobinsonDepartment of Laboratory Medicine and Pathobiology; University of Toronto; Toronto, Ontario, Canada.
Melody Pai
Jeff C Liu
Frederick Vizeacoumar
Thomas Sun
Sean E Egan
Alessandro Datti
Jing Huang
Eldad Zacksenhaus
Institute of Molecular Biology · BGLunenfeld-Tanenbaum Research Institute · CAUniversity of Toronto · CAHospital for Sick Children · CAMount Sinai Hospital · CAUniversity Health Network · CA

Funding

UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
Exploiting TOR Signaling for Cancer Drug DiscoveryR01CA124974 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HUANG, JING · 2007 to 2011
$1.5M
NCI NIH HHS R01 CA124974NIGMS NIH HHS T32 GM007185
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) represents an aggressive subtype, for which radiation and chemotherapy are the only options. Here we describe the identification of disulfiram, an FDA-approved drug used to treat alcoholism, as well as the related compound thiram, as the most potent growth inhibitors following high-throughput screens of 3185 compounds against multiple TNBC cell lines. The average IC50 for disulfiram was ~300 nM. Drug affinity responsive target stability (DARTS) analysis identified IQ motif-containing factors IQGAP1 and MYH9 as direct binding targets of disulfiram. Indeed, knockdown of these factors reduced, though did not completely abolish, cell growth. Combination treatment with 4 different drugs commonly used to treat TNBC revealed that disulfiram synergizes most effectively with doxorubicin to inhibit cell growth of TNBC cells. Disulfiram and doxorubicin cooperated to induce cell death as well as cellular senescence, and targeted the ESA(+)/CD24(-/low)/CD44(+) cancer stem cell population. Our results suggest that disulfiram may be repurposed to treat TNBC in combination with doxorubicin.

Indexed as

Antigens, NeoplasmAntineoplastic AgentsApoptosisCD24 AntigenCell Adhesion MoleculesCell Line, TumorCellular SenescenceDisulfiramDoxorubicinDrug SynergismEpithelial Cell Adhesion MoleculeFemaleHigh-Throughput Screening AssaysHumansHyaluronan ReceptorsMCF-7 CellsAntigens, NeoplasmAntineoplastic AgentsCD24 AntigenCell Adhesion MoleculesDisulfiramDoxorubicinEpithelial Cell Adhesion MoleculeHyaluronan ReceptorsIQ motif containing GTPase activating protein 1Molecular Motor ProteinsMYH9 protein, humanMyosin Heavy Chainsras GTPase-Activating Proteinscancer stem cellsdisulfiramhigh-throughput screensIQGAP1MYH9triple-negative breast cancer

Identifiers

PMID23974104
PMCPMC3875676
OpenAlexW2085936959

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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.