Evidence map›Paper›PMID 38194275›Full record

ArticleThe Journal of clinical investigation2024

Neutrophil extracellular traps induced by chemotherapy inhibit tumor growth in murine models of colorectal cancer.

Yamu Li, Sulin Wu, Yiqing Zhao, Trang Dinh, Dongxu Jiang, J Eva Selfridge, George Myers, Yuxiang Wang, Xuan Zhao, Suzanne Tomchuck and 15 more

Open access · goldAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
15.6field-weighted citation impact, top 1% 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

67 citing papers in PubMed, 65 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Neutrophil extracellular traps (NETosis) in gynecologic cancers: from pathogenesis to therapeutic opportunities: a narrative review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  10. Review
  11. Article
  12. Macrophage Extracellular Traps in Immunity and Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Neutrophil extracellular traps in cancer.Nature reviews. Cancer · 2026
    Review
  19. Review
  20. Article

7 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

25 authors at 5 institutions in 1 country.

Yamu LiDepartment of Genetics and Genome Sciences.
Sulin WuDepartment of Genetics and Genome Sciences.
Yiqing ZhaoDepartment of Genetics and Genome Sciences.
Trang DinhDepartment of Genetics and Genome Sciences.
Dongxu JiangDepartment of Genetics and Genome Sciences.
J Eva SelfridgeDepartment of Genetics and Genome Sciences.
George MyersDepartment of Pathology.
Yuxiang WangDepartment of Genetics and Genome Sciences.
Xuan ZhaoDepartment of Genetics and Genome Sciences.
Suzanne TomchuckDepartment of Pediatrics, and.
George DubyakDepartment of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio. USA.
Richard T LeeDepartment of Internal Medicine.
Bassam EstfanTaussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Marc ShapiroTaussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Suneel KamathTaussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Amr MohamedDepartment of Internal Medicine.
Stanley Ching-Cheng HuangCase Comprehensive Cancer Center.
Alex Y HuangDepartment of Pediatrics, and.
Ronald ConlonDepartment of Genetics and Genome Sciences.
Smitha KrishnamurthiTaussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Jennifer EadsDepartment of Internal Medicine.
Joseph E WillisDepartment of Pathology.
Alok A KhoranaTaussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.
David BajorDepartment of Internal Medicine.
Zhenghe WangDepartment of Genetics and Genome Sciences.
Case Comprehensive Cancer CenterCase Western Reserve University · USCleveland Clinic · USUniversity Hospitals Seidman Cancer Center · USPediatrics and Genetics · US

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARK R CHANCE · 1987 to 2026
$142.3M
Targeting 15-PGDH in Colon Cancer Prognosis, Prediction, Treatment and PreventionP50CA150964 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI MARKOWITZ, SANFORD D. · 2011 to 2022
$24.6M
Mechanisms of metabolic reprogramming by PIK3CA oncogenic mutationsR01CA196643 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI Zhenghe Wang · 2016 to 2026
$3.1M
Role of Erbb3 kinase activity in colorectal tumorigenesis.R01CA256791 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI WANG, ZHENGHE · 2021 to 2025
$2.5M
Role of PTPRT in colon cancer progression and metastasisR01CA260629 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI WANG, ZHENGHE · 2022 to 2025
$2.2M
Mechanisms of PIK3CA helical domain mutations driving colorectal tumorigenesisR01CA264320 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI WANG, ZHENGHE · 2021 to 2025
$2.0M
NCI NIH HHS P30 CA043703NCI NIH HHS P50 CA150964NCI NIH HHS R01 CA196643NCI NIH HHS R01 CA256791NCI NIH HHS R01 CA260629NCI NIH HHS R01 CA264320
6 · The paper itself

Abstract

Neutrophil extracellular traps (NETs), a web-like structure of cytosolic and granule proteins assembled on decondensed chromatin, kill pathogens and cause tissue damage in diseases. Whether NETs can kill cancer cells is unexplored. Here, we report that a combination of glutaminase inhibitor CB-839 and 5-FU inhibited the growth of PIK3CA-mutant colorectal cancers (CRCs) in xenograft, syngeneic, and genetically engineered mouse models in part through NETs. Disruption of NETs by either DNase I treatment or depletion of neutrophils in CRCs attenuated the efficacy of the drug combination. Moreover, NETs were present in tumor biopsies from patients treated with the drug combination in a phase II clinical trial. Increased NET levels in tumors were associated with longer progression-free survival. Mechanistically, the drug combination induced the expression of IL-8 preferentially in PIK3CA-mutant CRCs to attract neutrophils into the tumors. Further, the drug combination increased the levels of ROS in neutrophils, thereby inducing NETs. Cathepsin G (CTSG), a serine protease localized in NETs, entered CRC cells through the RAGE cell surface protein. The internalized CTSG cleaved 14-3-3 proteins, released BAX, and triggered apoptosis in CRC cells. Thus, our studies illuminate a previously unrecognized mechanism by which chemotherapy-induced NETs kill cancer cells.

Indexed as

Colorectal NeoplasmsExtracellular TrapsAnimalsClass I Phosphatidylinositol 3-KinasesDisease Models, AnimalDrug CombinationsHumansMiceClass I Phosphatidylinositol 3-KinasesDrug CombinationsColorectal cancerNeutrophilsOncogenesOncology

Identifiers

PMID38194275
PMCPMC10904055
OpenAlexW4390751260

What OpenQuestion holds

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LicenceCC BY
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.