Evidence map›Paper›PMID 35466502›Full record

ArticleCancer science2022

Ferroptosis is induced by lenvatinib through fibroblast growth factor receptor-4 inhibition in hepatocellular carcinoma.

Norifumi Iseda, Shinji Itoh, Katsuya Toshida, Takahiro Tomiyama, Akinari Morinaga, Masahiro Shimokawa, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Takeo Toshima and 4 more

Abstract read
In one paragraph

Article in Cancer science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing 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

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

  1. Pooled it
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  15. Review
  16. Ferroptosis: biology and role in liver disease.Journal of gastroenterology · 2025
    Review
  17. Article
  18. Review
  19. Article
  20. Immunometabolic Targets in CD8Liver cancer · 2025
    Review

21 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

14 authors.

Norifumi IsedaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shinji ItohDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.ORCID https://orcid.org/0000-0003-0382-2520
Katsuya ToshidaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takahiro TomiyamaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Akinari MorinagaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Masahiro ShimokawaDepartment of Molecular Oncology, Tokyo medical and dental university, Tokyo, Japan.ORCID https://orcid.org/0000-0002-8645-4112
Tomonari ShimagakiDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Huanlin WangDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takeshi KuriharaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Takeo ToshimaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.ORCID https://orcid.org/0000-0003-4019-8288
Yoshihiro NagaoDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Noboru HaradaDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Tomoharu YoshizumiDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Masaki MoriDepartment of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Funding

Japan Society for the Promotion of Science 19K09198Japan Society for the Promotion of Science JP-16K10576
6 · The paper itself

Abstract

The tyrosine kinase inhibitor lenvatinib is used to treat advanced hepatocellular carcinoma (HCC). Ferroptosis is a type of cell death characterized by the iron-dependent accumulation of lethal lipid reactive oxygen species (ROS). Nuclear factor erythroid-derived 2-like 2 (Nrf2) protects HCC cells against ferroptosis. However, the mechanism of lenvatinib-induced cytotoxicity and the relationships between lenvatinib resistance and Nrf2 are unclear. Thus, we investigated the relationship between lenvatinib and ferroptosis and clarified the involvement of Nrf2 in lenvatinib-induced cytotoxicity. Cell viability, lipid ROS levels, and protein expression were measured using Hep3B and HuH7 cells treated with lenvatinib or erastin. We examined these variables after silencing fibroblast growth factor receptor-4 (FGFR4) or Nrf2 and overexpressing-Nrf2. We immunohistochemically evaluated FGFR4 expression in recurrent lesions after resection and clarified the relationship between FGFR4 expression and lenvatinib efficacy. Lenvatinib suppressed system X

Indexed as

Carcinoma, HepatocellularFerroptosisFibroblast Growth Factor 4Liver NeoplasmsPhenylurea CompoundsQuinolinesHumansLipidsNF-E2-Related Factor 2Reactive Oxygen SpeciesFGF4 protein, humanFibroblast Growth Factor 4lenvatinibLipidsNF-E2-Related Factor 2Phenylurea CompoundsQuinolinesReactive Oxygen Specieslipid ROSliver cancernuclear factor erythroid-derived 2-like 2oxidative stresstyrosine kinase inhibitor

Identifiers

PMID35466502
PMCPMC9277415

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.