Evidence mapPaperPMID 38816352Full record

ArticleNature communications2024

Statin prevents cancer development in chronic inflammation by blocking interleukin 33 expression.

Jong Ho Park, Mahsa Mortaja, Heehwa G Son, Xutu Zhao, Lauren M Sloat, Marjan Azin, Jun Wang, Michael R Collier, Krishna S Tummala, Anna Mandinova and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
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

32 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  13. 27-Hydroxycholesterol in cancer development and drug resistance.Journal of enzyme inhibition and medicinal chemistry · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Jong Ho ParkCenter for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Mahsa MortajaCenter for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Heehwa G SonCenter for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Xutu ZhaoCenter for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0003-0856-3481
Lauren M SloatCenter for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1315-1302
Marjan AzinCenter for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Jun WangCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Michael R CollierDepartment of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Krishna S TummalaKrantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Anna MandinovaCutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nabeel BardeesyKrantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3867-0416
Yevgeniy R SemenovDepartment of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Mari Mino-KenudsonDepartment of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9092-2265
Shadmehr DemehriCenter for Cancer Immunology, Krantz Family Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. sdemehri1@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-7913-2641

Funding

Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · 2022 to 2025
$5.6M
Project 3-Cancer cell interaction with oncogenic type 1 collagen in PDACP01CA117969 · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2025 to 2025
$2.4M
Functions of the LKB1 tumor suppressor in control in metabolism and epigeneticsR01CA215498 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI NABEEL El-BARDEESY · 2022 to 2022
$471k
Burroughs Wellcome Fund (BWF) CAMSNCI NIH HHS P01 CA117969NCI NIH HHS P50 CA127003NCI NIH HHS R01 CA215498NCI NIH HHS R01 CA219670NIAMS NIH HHS K08 AR068619NIAMS NIH HHS R01 AR076013NIGMS NIH HHS T32 GM144273Sidney Kimmel Foundation ScholarU.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) K08AR068619U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) R01AR076013
6 · The paper itself

Abstract

Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.

Indexed as

Hydroxymethylglutaryl-CoA Reductase InhibitorsInterferon Regulatory Factor-3Interleukin-33Pancreatic NeoplasmsProtein Serine-Threonine KinasesQuinolinesSignal TransductionAnimalsFemaleHumansInflammationMaleMevalonic AcidMiceMice, Inbred C57BLMice, KnockoutHydroxymethylglutaryl-CoA Reductase InhibitorsIL33 protein, humanIl33 protein, mouseInterferon Regulatory Factor-3Interleukin-33Irf3 protein, mouseMevalonic AcidpitavastatinProtein Serine-Threonine KinasesQuinolinesTBK1 protein, humanTbk1 protein, mouseToll-Like Receptor 3Toll-Like Receptor 4

Identifiers

PMID38816352
PMCPMC11139893

What Socratic 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 Socratic graph.