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Targeting ferroptosis in Helicobacter pylori‑associated gastric cancer development: From molecular mechanisms to application prospects (Review)

  • Authors:
    • Chen-Yi Wang
    • Meng-Hui Wang
    • Chuan Xie
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 4
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    Published online on: November 5, 2025
       https://doi.org/10.3892/ijo.2025.5817
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Abstract

Gastric cancer (GC) has a high incidence, resistance to chemotherapeutic drugs and a bleak prognosis. Helicobacter pylori (H. pylori) can promote GC development through Correa's cascade by impacting various forms of programmed cell death (PCD). As an iron‑dependent form of PCD, ferroptosis has emerged as a major focus in biomedical research. Notably, there have been developments in elucidating the mechanisms underlying ferroptosis dysregulation throughout Correa's cascade. On one hand, targeting ferroptosis may provide a promising direction for the development of drugs for chronic atrophic gastritis (CAG) and intestinal metaplasia (IM). On the other hand, targeting ferroptosis in GC may be a potential option to overcome the challenges in conventional therapies such as resistance to chemotherapy. Consequently, the present review aims to deliver a comprehensive understanding of the mechanisms underlying ferroptosis dysregulation in H. pylori‑associated GC and summarize the latest progress of ferroptosis‑related studies in CAG, IM and GC. The present study identifies key regulators of ferroptosis at distinct pathological stages, thereby providing insight of novel strategies for the management of precancerous lesion‑related diseases and GC.
View Figures

Figure 1

Potential ferroptosis-related
strategies in cancer management. PUFA, polyunsaturated fatty
acid.

Figure 2

H. pylori can cause the
dysregulation of apoptosis, autophagy, pyroptosis and necroptosis
through various pathogenic virulence factors. VacA, vacuolar cell
toxin; CagA, cytotoxin-associated gene A; OipA, outer inflammatory
protein A; TRAP1, tumor necrosis factor receptor-associated protein
1; RNS, reactive nitrogen species; Bcl-2, B-cell lymphoma-2; Bax,
Bcl-2-associated X; T4SS, type IV secretion system; RIPK3, receptor
interacting Serine/Threonine kinase 3; ASC, apoptosis-associated
speck-like protein containing a CARD; NLRC4, NLR family CARD
domain-containing protein 4; SMO, spermine oxidase; Apaf-1,
apoptotic protease activating factor-1.

Figure 3

H. pylori can bi-directively
regulate ferroptosis through the virulence factors CagA and OMVs.
PHKG2, phosphorylase kinase G2; ALOX5, arachidonate 5-lipoxygenase;
OMVs, outer membrane vesicles; TFRC/TFR1, transferrin
receptor/transferrin receptor protein 1; LPCAT3,
lysophosphatidylcholine acyltransferase 3; GBA1,
glucocerebrosidase; STEAP3, six-transmembrane epithelial antigen of
the prostate 3; SRF, serum response factor; AGPS, alkylglycerone
phosphate synthase; AGPAT3, 1-acylglycerol-3-phosphate
O-acyltransferase 3; PUFA-ePLs, polyunsaturated ether
phospholipids.

Figure 4

Several compounds have been reported
to be able to exert therapeutic effects in the stages of CAG, IM
and GC. (A) XLHZ plays a therapeutic role in CAG by inhibiting
ferroptosis. (B) Ranolrazole inhibits IM progression by promoting
ferroptosis. (C) Compounds a2, PB, Quer and DHA exert antitumor
effects by promoting ferroptosis, whereas LF3 and W1131 increase
chemotherapy sensitivity by promoting ferroptosis. XLHZ,
Xianglianhuazhuo; YY1, Yin Yang 1; PB, polyphyllin B; Quer,
quercetin; FTH1, ferritin heavy chain 1; CDX2, caudal type homeobox
transcription factor 2; MUC2, mucin 2; Fer-1, ferrostatin-1; CREB,
cAMP-response element binding protein; TCF4, transcription factor
4; NRF2, nuclear factor erythroid 2-related factor 2; Camk2,
calcium/calmodulin-dependent protein kinase 2; DRP1,
dynamin-related protein 1.
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Wang C, Wang M and Xie C: Targeting ferroptosis in <em>Helicobacter pylori</em>‑associated gastric cancer development: From molecular mechanisms to application prospects (Review). Int J Oncol 68: 4, 2026.
APA
Wang, C., Wang, M., & Xie, C. (2026). Targeting ferroptosis in <em>Helicobacter pylori</em>‑associated gastric cancer development: From molecular mechanisms to application prospects (Review). International Journal of Oncology, 68, 4. https://doi.org/10.3892/ijo.2025.5817
MLA
Wang, C., Wang, M., Xie, C."Targeting ferroptosis in <em>Helicobacter pylori</em>‑associated gastric cancer development: From molecular mechanisms to application prospects (Review)". International Journal of Oncology 68.1 (2026): 4.
Chicago
Wang, C., Wang, M., Xie, C."Targeting ferroptosis in <em>Helicobacter pylori</em>‑associated gastric cancer development: From molecular mechanisms to application prospects (Review)". International Journal of Oncology 68, no. 1 (2026): 4. https://doi.org/10.3892/ijo.2025.5817
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Spandidos Publications style
Wang C, Wang M and Xie C: Targeting ferroptosis in <em>Helicobacter pylori</em>‑associated gastric cancer development: From molecular mechanisms to application prospects (Review). Int J Oncol 68: 4, 2026.
APA
Wang, C., Wang, M., & Xie, C. (2026). Targeting ferroptosis in <em>Helicobacter pylori</em>‑associated gastric cancer development: From molecular mechanisms to application prospects (Review). International Journal of Oncology, 68, 4. https://doi.org/10.3892/ijo.2025.5817
MLA
Wang, C., Wang, M., Xie, C."Targeting ferroptosis in <em>Helicobacter pylori</em>‑associated gastric cancer development: From molecular mechanisms to application prospects (Review)". International Journal of Oncology 68.1 (2026): 4.
Chicago
Wang, C., Wang, M., Xie, C."Targeting ferroptosis in <em>Helicobacter pylori</em>‑associated gastric cancer development: From molecular mechanisms to application prospects (Review)". International Journal of Oncology 68, no. 1 (2026): 4. https://doi.org/10.3892/ijo.2025.5817
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