Evidence map›Paper›PMID 39002022›Full record

ArticleCancer chemotherapy and pharmacology2024

Ferroptosis - a potential feature underlying neratinib-induced colonic epithelial injury.

Triet P M Nguyen, Susan L Woods, Kate R Secombe, Simon Tang, Aurelia S Elz, Scott Ayton, John Finnie, Aadya Nagpal, Normand Pouliot, Joanne M Bowen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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.

Triet P M NguyenSchool of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia. phuminhtrietthomas.nguyen@unimelb.edu.au.
Susan L WoodsAdelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.
Kate R SecombeSchool of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia.
Simon TangSchool of Life and Environmental Sciences, The University of Sydney, Sydney, Australia.
Aurelia S ElzSchool of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia.
Scott AytonThe Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia.
John FinnieDiscipline of Anatomy and Pathology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Aadya NagpalOlivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
Normand PouliotOlivia Newton-John Cancer Research Institute, Heidelberg, VIC, Australia.
Joanne M BowenSchool of Biomedicine, The University of Adelaide, Adelaide, South Australia, Australia. joanne.bowen@adelaide.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeNeratinib, a small-molecule tyrosine kinase inhibitor (TKI) that irreversibly binds to human epidermal growth factor receptors 1, 2 and 4 (HER1/2/4), is an approved extended adjuvant therapy for patients with HER2-amplified or -overexpressed (HER2-positive) breast cancers. Patients receiving neratinib may experience mild-to-severe symptoms of gut toxicity including abdominal pain and diarrhoea. Despite being a highly prevalent complication in gut health, the biological processes underlying neratinib-induced gut injury, especially in the colon, remains unclear.

methodsReal-time quantitative polymerase chain reaction (RT-qPCR) and histology were integrated to study the effect of, and type of cell death induced by neratinib on colonic tissues collected from female Albino Wistar rats dosed with neratinib (50 mg/kg) daily for 28 days. Additionally, previously published bulk RNA-sequencing and CRISPR-screening datasets on human glioblastoma SF268 cell line and glioblastoma T895 xenograft, and mouse TBCP1 breast cancer cell line were leveraged to elucidate potential mechanisms of neratinib-induced cell death.

resultsThe severity of colonic epithelial injury, especially degeneration of surface lining colonocytes and infiltration of immune cells, was more pronounced in the distal colon than the proximal colon. Sequencing showed that apoptotic gene signature was enriched in neratinib-treated SF268 cells while ferroptotic gene signature was enriched in neratinib-treated TBCP1 cells and T895 xenograft. However, we found that ferroptosis, but less likely apoptosis, was a potential histopathological feature underlying colonic injury in rats treated with neratinib.

conclusionFerroptosis is a potential feature of neratinib-induced colonic injury and that targeting molecular machinery governing neratinib-induced ferroptosis may represent an attractive therapeutic approach to ameliorate symptoms of gut toxicity.

Indexed as

ColonFerroptosisQuinolinesRats, WistarAnimalsCell Line, TumorFemaleHumansMiceProtein Kinase InhibitorsRatsneratinibProtein Kinase InhibitorsQuinolinesColonic injuryFerroptosisGut toxicityNeratinib

Identifiers

PMID39002022
PMCPMC11438713

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