REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1581928
This article is part of the Research TopicFerroptosis and regulation mechanism in the tumor immune microenvironment for tumor progression and treatmentView all 9 articles
Ferroptosis and Gastric Cancer: From Molecular Mechanisms to Clinical Implications
Provisionally accepted
- 1Hohhot Mongolian Hospital of Traditional Chinese Medicine, Hohhot, Inner Mongolia Autonomous Region, China
- 2College of Traditional Chinese Medicine, Inner Mongolia Medical University, Huhhot, Inner Mongolia Autonomous Region, China
- 3Inner Mongolia Autonomous Region Traditional Chinese Medicine Hospital, Hohhot, Inner Mongolia Autonomous Region, China
- 4Baotou Medical College, Baotou, China
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Gastric cancer, one of the leading causes of cancer-related mortality globally, faces challenges in treatment due to limitations in surgery, chemotherapy resistance, and high recurrence rates. Ferroptosis, an iron-dependent form of cell death, induces cell membrane rupture through dysregulated iron metabolism, lipid peroxidation,and the accumulation of reactive oxygen species (ROS), offering a promising therapeutic avenue for gastric cancer treatment.This article systematically explores the core mechanisms of ferroptosis, including iron overload catalyzing lipid peroxidation via the Fenton reaction, dysregulation of antioxidant systems (such as GPX4 and FSP1), and their associations with gastric cancer cell proliferation, metastasis, and resistance. Studies indicate that abnormalities in iron metabolism in gastric cancer cells, such as upregulation of TFR1 and dysregulated ferritin storage, significantly promote ferroptosis sensitivity, while ferroptosis inducers (such as Erastin and RSL3) can enhance chemotherapy sensitivity and reverse resistance by inhibiting GPX4 or system Xc-. Preclinical experiments confirm that targeting ferroptosis-related pathways (such as the USP7/SCD axis and ABCC2-mediated glutathione efflux) effectively inhibits tumor growth and metastasis. However, the dual-edged effect of ferroptosis warrants caution regarding its oxidative damage risk to normal tissues and potential pro-metastatic mechanisms. This article further proposes the potential of ferroptosis biomarkers (such as 4-HNE and GPX4) in early diagnosis and prognosis assessment of gastric cancer and emphasizes the need for precision medicine to optimize ferroptosis-targeted strategies, balancing efficacy and safety. Ferroptosis opens a new avenue for gastric cancer treatment, but its clinical translation still requires in-depth mechanistic exploration and personalized treatment plan design.
Keywords: gastric cancer, ferroptosis, Lipid Peroxidation, GPx4, treatment resistance
Received: 23 Feb 2025; Accepted: 22 Jul 2025.
Copyright: © 2025 Zhao, Ao, So, Wei, Zhen, Zhang, Qing, Li and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Gailan Zhou, Hohhot Mongolian Hospital of Traditional Chinese Medicine, Hohhot, Inner Mongolia Autonomous Region, China
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