Evidence map›Paper›PMID 36711701›Full record

ArticleResearch square2023

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

Jong Ho Park, Mahsa Mortaja, Heehwa Son, Marjan Azin, Jun Wang, Michael Collier, Anna Mandinova, Yevgeniy Semenov, Mari Mino-Kenudson, Shadmehr Demehri

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed, 3 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 1 country.

Jong Ho ParkMassachusetts General Hospital.
Mahsa MortajaMassachusetts General Hospital.
Heehwa SonMassachusetts General Hospital.
Marjan AzinMassachusetts General Hospital.
Jun WangMassachusetts General Hospital.
Michael CollierMassachusetts General Hospital.
Anna MandinovaMassachusetts General Hospital.
Yevgeniy SemenovMassachusetts General Hospital.ORCID 0000-0002-7387-3094
Mari Mino-KenudsonMassachusetts General Hospital.ORCID 0000-0002-9092-2265
Shadmehr DemehriMassachusetts General Hospital.ORCID 0000-0002-7913-2641
Massachusetts General Hospital · US

Funding

Immunotherapy for Skin Cancer Precursors to Prevent Skin CancerR01AR076013 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DEMEHRI, SHADMEHR · 2019 to 2023
$1.8M
The Role of Allergic Contact Dermatitis in Skin CarcinogenesisK08AR068619 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI DEMEHRI, SHADMEHR · 2015 to 2019
$753k
NIAMS NIH HHS K08 AR068619NIAMS NIH HHS R01 AR076013
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 the 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. FDA-approved drug library screen identified pitavastatin as an effective IL-33 inhibitor by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevented chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. IRF3-IL-33 axis was highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlated with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3 signaling pathway suppresses IL-33 expression and cancer-prone chronic inflammation. Statins present a safe and effective therapeutic strategy to prevent chronic inflammation and its cancer sequela.

Indexed as

cancer preventionchronic inflammationchronic pancreatitisInterleukin-33pancreatic cancerpitavastatinTBK1-IRF3 pathway

Identifiers

PMID36711701
PMCPMC9882616
OpenAlexW4315703261

What Socratic holds

Textmetadata
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 Socratic graph.