Ferroptosis and oxidative stress crosstalk in tumor microenvironment: Mechanisms and targeting strategies

Ping Zhang

1,#

Chaoting Zhou

4,#

Chen Yang

2,#

Huanjuan Li

Xueying Ren

Yi Lu

Feifan Pan

Jun Xia

2,*

Jing Du

2,*

Yanchun Li

3,*

Affiliation +

*Correspondence to: Jun Xia, Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China. E-mail: andisky_005@126.com
Jing Du, Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China. E-mail: dujing1@hmc.edu.cn
Yanchun Li, Department of Clinical Laboratory, Affiliated Hangzhou First People’s Hospital, School of Medical, Westlake University, Hangzhou 310006, Zhejiang, China. E-mail: lycmed@163.com

Ferroptosis Oxid Stress. 2027;3:202635. 10.70401/fos.2026.0049

Received: July 13, 2026Accepted: October 09, 2026Published: October 10, 2026

This manuscript is made available in its unedited form to allow early access to the reported findings. Further editing will be completed before final publication. As such, the content may include errors, and standard legal disclaimers are applicable.

Abstract

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is intricately linked with oxidative stress through shared regulatory nodes and reciprocal amplification loops. Although ferroptosis and oxidative stress have each been extensively investigated, their bidirectional crosstalk, together with its consequences for the tumor microenvironment, has yet to be systematically elucidated. On this basis, this review proposes and systematically dissects a “ferroptosis-oxidative stress-tumor microenvironment” triad, focusing on its bidirectional interaction network and therapeutic translational value. We analyze the driving mechanisms underlying the mutually amplifying loop between the two processes, including iron metabolism, lipid peroxidation cascades, antioxidant defense, and organelle function. Within the tumor microenvironment, this interplay drives context-dependent remodeling of immune cell function, cancer-associated fibroblast activity, angiogenesis, and tumor heterogeneity. Furthermore, this review evaluates emerging therapeutic strategies that target ferroptosis and oxidative stress within the TME, and outlines the obstacles hindering clinical translation and future directions. A deep understanding of the “ferroptosis-oxidative stress-tumor microenvironment” triad will advance our fundamental understanding of the execution and regulatory mechanisms of ferroptosis, and lay a theoretical foundation for the future development of precision therapeutic strategies centered on ferroptosis.

Keywords

Ferroptosis, oxidative stress, tumor microenvironment, therapeutic strategies

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Zhang P, Zhou C, Yang C, Li H, Ren X, Lu Y, et al. Ferroptosis and oxidative stress crosstalk in tumor microenvironment: Mechanisms and targeting strategies. Ferroptosis Oxid Stress. 2027;3:202635. https://doi.org/10.70401/fos.2026.0049

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Ferroptosis and Oxidative Stress

Ferroptosis and oxidative stress crosstalk in tumor microenvironment: Mechanisms and targeting strategies

Ping Zhang

Chaoting Zhou

Chen Yang

Huanjuan Li

Xueying Ren

Yi Lu

Feifan Pan

Jun Xia

Jing Du

Yanchun Li

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Ferroptosis and Oxidative Stress

Ferroptosis and oxidative stress crosstalk in tumor microenvironment: Mechanisms and targeting strategies

Ping Zhang

Chaoting Zhou

Chen Yang

Huanjuan Li

Xueying Ren

Yi Lu

Feifan Pan

Jun Xia

Jing Du

Yanchun Li

Abstract

Keywords

References

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