Evidence map›Paper›PMID 36230739›Full record

ArticleCancers2022

Novel Methods of Targeting IL-1 Signalling for the Treatment of Breast Cancer Bone Metastasis.

Jiabao Zhou, Jennifer M Down, Christopher N George, Jessica Murphy, Diane V Lefley, Claudia Tulotta, Marwa A Alsharif, Michael Leach, Penelope D Ottewell

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–field-weighted citation impact
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

12 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Mouse Models of Breast Cancer Bone Metastasis.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  5. Review
  6. Review
  7. Article
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  9. Article
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  11. Article
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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

9 authors.

Jiabao ZhouAcademic Unit of Clinical Oncology, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield S10 2RX, UK.ORCID 0000-0003-1108-6391
Jennifer M DownAcademic Unit of Clinical Oncology, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
Christopher N GeorgeAcademic Unit of Clinical Oncology, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
Jessica MurphyAcademic Unit of Clinical Oncology, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
Diane V LefleyAcademic Unit of Clinical Oncology, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
Claudia TulottaAcademic Unit of Clinical Oncology, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
Marwa A AlsharifAcademic Unit of Clinical Oncology, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield S10 2RX, UK.
Michael LeachSchool of Science, University of Greenwich at Medway, Chatham ME4 4TB, UK.
Penelope D OttewellAcademic Unit of Clinical Oncology, Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield S10 2RX, UK.ORCID 0000-0002-4826-0771

Funding

Medical Research Council MR/P000096/1
6 · The paper itself

Abstract

Breast cancer bone metastasis is currently incurable. Evidence suggests that inhibiting IL-1 signalling with the IL1R antagonist, Anakinra, or the IL1β antibody, Canakinumab, prevents metastasis and almost eliminates breast cancer growth in the bone. However, these drugs increase primary tumour growth. We, therefore, investigated whether targeting other members of the IL-1 pathway (Caspase-1, IL1β or IRAK1) could reduce bone metastases without increasing tumour growth outside of the bone. Inhibition of IL-1 via MLX01 (IL1β secretion inhibitor), VRT043198/VX765 (Caspase-1 inhibitor), Pacritinib (IRAK1 inhibitor) or Anakinra (IL1R antagonist) on tumour cell viability, migration and invasion were assessed in mouse mammary E0771 and Py8119 cells in vitro and on primary tumour growth, spontaneous metastasis and metastatic outgrowth in vivo. In vitro, Inhibition of IL-1 signalling by MLX01, VRT043198 and Anakinra reduced migration of E0771 and Py8119 cells and reversed tumour-derived IL1β induced-increased invasion and migration towards bone cells. In vivo, VX765 and Anakinra significantly reduced spontaneous metastasis and metastatic outgrowth in the bone, whereas MLX01 reduced primary tumour growth and bone metastasis. Pacritinib had no effect on metastasis in vitro or in vivo. Targeting IL-1 signalling with small molecule inhibitors may provide a new therapeutic strategy for breast cancer bone metastasis.

Indexed as

bone metastasisbreast cancerIL1βmouse models

Identifiers

PMID36230739
PMCPMC9561984

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.