Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer

Sep 23, 2026

Uploaded by Levi

Ferroptosis is a regulated cell-death process driven by iron accumulation and lipid peroxidation. After being established as a recognized modality of regulated cell death, it has gained strong momentum in cancer research due to its specific metabolic and redox requirements. Emerging systems-level studies indicate ferroptosis is shaped by metabolic reprogramming, gene/RNA regulation, and inter-organelle communication, while also reshaping immunity and the tumor microenvironment. Related genes and pathways are proposed as biomarkers for risk stratification, treatment selection, and imaging assessment. Translational strategies using small-molecule inducers, targeted inhibitors, and delivery systems aim to overcome therapeutic resistance, with emphasis on pancreatic cancer, and to support precision diagnostics and personalized interventions.

LanguageEnglish

CategoryHealthcare

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Pages26

Reading Time1 h 6 min

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Abstract

Introduction

Chen et al. Molecular Cancer (2026) 25:48 [https://doi.org/10.1186/s12943-025-02567-5](https://doi.org/10.1186/s12943-025-02567-5) Molecular Cancer REVIEW Open Access Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer Qun Chen1†, Fengyuan Liu1†, Yufeng Zhang1†, Lingtao Yan1, Yang Wu1, Dong Xu1, Pengfei Wu1*, Hao Yuan1* and Kuirong Jiang1* Abstract Ferroptosis is a regulated form of cell death driven by iron accumulation and lipid peroxidation. Since its recognition as a modality of regulated cell death, ferroptosis has attracted increasing attention in cancer research for its distinct metabolic and redox dependencies. Recent evidence suggests that ferroptosis arises from systems-level regulation integrating metabolic reprogramming, gene and RNA control, and inter-organelle communication, while simultaneously influencing immune remodeling and the tumor microenvironment. These processes collectively determine ferroptosis susceptibility and therapeutic response. Ferroptosis-related genes and pathways have also emerged as potential biomarkers for risk stratification, treatment prediction, and imaging-based assessment. Moreover, small-molecule inducers, targeted inhibitors, and delivery systems capable of modulating ferroptosis demonstrate translational potential to overcome therapeutic resistance across multiple malignancies, including pancreatic cancer. This review synthesizes recent mechanistic and translational advances, highlighting ferroptosis as a conceptual bridge between cellular metabolism and tumor therapy, and outlining perspectives for precision diagnostics and personalized interventions. Keywords Ferroptosis, Regulated cell death, Cancer metabolism, Molecular mechanism, Therapeutic significance, Translational medicine †Qun Chen, Fengyuan Liu andYufeng Zhang contributed equally to this work. *Correspondence: Pengfei Wu [wupengfei@njmu.edu.cn](wupengfei@njmu.edu.cn)[ ](wupengfei@njmu.edu.cn)Hao Yuan [yuanhao@njmu.edu.cn](yuanhao@njmu.edu.cn)[ ](yuanhao@njmu.edu.cn)Kuirong Jiang [jiangkuirong@njmu.edu.cn](jiangkuirong@njmu.edu.cn) 1Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China Introduction Ferroptosis, an iron-dependent form of regulated cell death (RCD) first described in 2012 by the Stockwell [1] and fomally recognized by the Nomenclature Committee on Cell Death (NCCD) in 2018 [2]. Its conceptual roots extend back to studies in the mid-20th century, when Eagle showed that mammalian cells rely on exogenous cysteine (Cys) for survival [3]. Subsequent work clarified the biochemical basis of this dependency as Bannai identified cystine and glutamate exchange through System Xc ⁻[4], glutamate inhibition of this transporter was found to cause oxidative cell death [5], and Schubert showed that vitamin E could prevent this outcome [6]. These findings defined the early metabolic framework of ferroptosis. In © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http

FAQs

What triggers ferroptosis in cancer cells?

Ferroptosis is driven by iron accumulation and lipid peroxidation, and is described as an iron-dependent regulated form of cell death.

How does ferroptosis connect metabolism to tumor biology?

Mechanistic evidence links ferroptosis susceptibility to systems-level control involving metabolic reprogramming, gene/RNA regulation, and inter-organelle communication, which also influences immune remodeling and the tumor microenvironment.

What translational tools are discussed for clinical use in pancreatic cancer?

The review highlights small-molecule inducers, targeted inhibitors, and delivery systems that modulate ferroptosis, aiming to overcome therapeutic resistance, alongside gene/pathway biomarkers for risk stratification, treatment prediction, and imaging-based assessment.

Sep 23, 2026

Uploaded by Levi