Evidence map›Paper›PMID 28875329›Full record

ArticleCancer immunology, immunotherapy : CII2018

The STAT3 inhibitor pyrimethamine displays anti-cancer and immune stimulatory effects in murine models of breast cancer.

Mohammad W Khan, Abdulrahman Saadalla, Ahmed H Ewida, Khalid Al-Katranji, Ghadier Al-Saoudi, Zachary T Giaccone, Fotini Gounari, Ming Zhang, David A Frank, Khashayarsha Khazaie

Open access · greenAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
4.5field-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

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.

  1. Role of STAT3 signaling pathway in breast cancer.Cell communication and signaling : CCS · 2020
    Pooled it
  2. STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review.Journal of experimental & clinical cancer research : CR · 2019
    Pooled it
  3. Review
  4. STAT3 axis in cancer and cancer stem cells: From oncogenesis to targeted therapies.Biochimica et biophysica acta. Reviews on cancer · 2025
    Review
  5. Article
  6. Pyrimethamine Triggers the Apoptotic Pathway in Mucoepidermoid Carcinoma in Cell-Based Models.Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology · 2025
    Article
  7. Article
  8. Review
  9. Article
  10. Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery.Journal of experimental & clinical cancer research : CR · 2024
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

1 more citing papers are in PubMed but not listed here.

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

10 authors at 5 institutions in 1 country.

Mohammad W KhanDepartment of Biology, San Diego State University, 5500 Campanile Drive, NLS-407, San Diego, CA, 92182, USA.
Abdulrahman SaadallaDepartment of Immunology, Department of Surgery, Mayo Clinic, Guggenheim 3-42B, Rochester, MN, 55905, USA.
Ahmed H EwidaRobert H. Lurie Comprehensive Cancer Center, Northwestern University, 303 East Superior Street, Lurie 3-250, Chicago, IL, 60611, USA.
Khalid Al-KatranjiRobert H. Lurie Comprehensive Cancer Center, Northwestern University, 303 East Superior Street, Lurie 3-250, Chicago, IL, 60611, USA.
Ghadier Al-SaoudiRobert H. Lurie Comprehensive Cancer Center, Northwestern University, 303 East Superior Street, Lurie 3-250, Chicago, IL, 60611, USA.
Zachary T GiacconeDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
Fotini GounariDepartment of Medicine, Section of Rheumatology, University of Chicago, JFK R314, 924 East 57th Street, MC 0930, Chicago, IL, 60637, USA.
Ming ZhangRobert H. Lurie Comprehensive Cancer Center, Northwestern University, 303 East Superior Street, Lurie 3-250, Chicago, IL, 60611, USA.
David A FrankDepartment of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA.
Khashayarsha KhazaieDepartment of Immunology, Department of Surgery, Mayo Clinic, Guggenheim 3-42B, Rochester, MN, 55905, USA. Khazaie@MAYO.edu.ORCID 0000-0002-7884-1817
Northwestern University · USDana-Farber Cancer Institute · USMayo Clinic · USSan Diego State University · USUniversity of Chicago · US

Funding

How beta-catenin expands Foxp3+RORgammat+ Pro-inflammatoryT-regulatory cells - RenewalR01AI108682 · NIAID · UNIVERSITY OF CHICAGO · PI GOUNARI, FOTINI, KHAZAIE, KHASHAYARSHA · 2014 to 2024
$5.1M
Role of Alcohol and Circadian Disruption in Inflammation and Colon CancerR01AA023417 · NIAAA · RUSH UNIVERSITY MEDICAL CENTER · PI KESHAVARZIAN, ALI, KHAZAIE, KHASHAYARSHA · 2014 to 2018
$2.0M
Proinflammatory T Regulatory Cells in Colon CancerR01CA160436 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KHAZAIE, KHASHAYARSHA · 2012 to 2017
$2.0M
NCI NIH HHS R01 CA160436NIAAA NIH HHS R01 AA023417NIAID NIH HHS R01 AI108682NIH HHS R01 AA023417-03NIH HHS R01 AI 108682-02NIH HHS R01CA160436-05
6 · The paper itself

Abstract

The transcription factor signal activator and transducer or transcription (STAT3), which regulates genes controlling proliferation, survival, and invasion, is activated inappropriately in many human cancers, including breast cancer. Activation of STAT3 can lead to both malignant cellular behavior and suppression of immune cell function in the tumor microenvironment. Through a chemical-biology screen, pyrimethamine (PYR), an FDA approved anti-microbial drug, was identified as an inhibitor of STAT3 function at concentrations known to be achieved safely in humans. We report that PYR shows therapeutic activity in two independent mouse models of breast cancer, with both direct tumor inhibitory and immune stimulatory effects. PYR-inhibited STAT3 activity in TUBO and TM40D-MB metastatic breast cancer cells in vitro and inhibited tumor cell proliferation and invasion into Matrigel basement membrane matrix. In tumor-transplanted mice, PYR had both direct and indirect tumor inhibitory effects. Tumor-bearing mice treated with PYR showed reduced STAT3 activation in tumor cells, attenuated tumor growth, and reduced tumor-associated inflammation. In addition, expression of Lamp1 by tumor infiltrating CD8

Indexed as

Adjuvants, ImmunologicAnimalsAnti-Infective AgentsAntineoplastic AgentsBreast NeoplasmsCD8-Positive T-LymphocytesCell Line, TumorCell ProliferationCytotoxicity, ImmunologicDisease Models, AnimalFemaleHumansLysosomal-Associated Membrane Protein 1Lysosomal Membrane ProteinsMiceMice, Inbred BALB CAdjuvants, ImmunologicAnti-Infective AgentsAntineoplastic AgentsLamp1 protein, mouseLysosomal-Associated Membrane Protein 1Lysosomal Membrane ProteinsPyrimethamineSTAT3 Transcription FactorBreast cancerImmunityMetastasisPyrimethamineSTAT3

Identifiers

PMID28875329
PMCPMC5783191
OpenAlexW2753005915

What OpenQuestion holds

Textmetadata
LicenceTDM
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.