The Role of Ferroptosis in Lung Cancer and Its Immunotherapeutic Targeting Strategy

Authors

  • Yinuo Gao

DOI:

https://doi.org/10.54097/388s4238

Keywords:

Ferroptosis, lung cancer, GPX4, reactive oxygen species, Nrf2 signaling pathway.

Abstract

Ferroptosis, an iron-dependent mode of cell death, exhibits unique potential in lung cancer therapy through the mechanisms of lipid peroxidation accumulation and glutathione peroxidase 4 (GPX4) inactivation. Lung cancer cells are highly sensitive to ferroptosis due to metabolic abnormalities and elevated levels of reactive oxygen species (ROS), in which the targeted inhibition of GPX4 and the regulation of the Nrf2 signaling pathway become key molecular mechanisms. Ferroptosis not only directly induces tumor cell death, but also significantly enhances the immunotherapeutic effect by releasing tumor antigens and remodeling the immunosuppressive microenvironment. However, the non-specific toxicity of ferroptosis inducers, drug resistance due to tumor heterogeneity, and the efficiency of targeted delivery still need to be addressed. In this paper, we will systematically explore the synergistic mechanism of ferroptosis and immunotherapy, and propose that the development of microenvironment-responsive drug delivery systems and combined therapeutic strategies is the direction of future breakthroughs. It provides a new idea for ferroptosis-targeted therapy to overcome immunotherapy resistance in lung cancer, but its clinical translation needs to be continuously explored in the in-depth analysis of the mechanism and technological innovation.

Downloads

Download data is not yet available.

References

[1] Li, J., et al., Ferroptosis: past, present and future. Cell Death Dis, 2020. 11 (2): p. 88.

[2] Chen, X., et al., Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol, 2021. 18 (5): p. 280-296.

[3] Wang, H., et al., Mitochondria regulation in ferroptosis. Eur J Cell Biol, 2020. 99 (1): p. 151058.

[4] Jiang, X., B.R. Stockwell, and M. Conrad, Ferroptosis: mechanisms, biology and role in disease. Nat Rev Mol Cell Biol, 2021. 22 (4): p. 266-282.

[5] Zi, Y., et al., Cigarette smoke induces the ROS accumulation and iNOS activation through deactivation of Nrf-2/SIRT3 axis to mediate the human bronchial epithelium ferroptosis. Free Radic Biol Med, 2023. 200: p. 73-86.

[6] Cai, S., et al., Trabectedin induces ferroptosis via regulation of HIF-1α/IRP1/TFR1 and Keap1/Nrf2/GPX4 axis in non-small cell lung cancer cells. Chem Biol Interact, 2023. 369: p. 110262.

[7] Zou, J., et al., Ferroptosis in Non-Small Cell Lung Cancer: Progression and Therapeutic Potential on It. Int J Mol Sci, 2021. 22 (24).

[8] Zhou, C., et al., Timosaponin AIII promotes non-small-cell lung cancer ferroptosis through targeting and facilitating HSP90 mediated GPX4 ubiquitination and degradation. Int J Biol Sci, 2023. 19 (5): p. 1471-1489.

[9] Zhang, C., et al., Corosolic acid inhibits EMT in lung cancer cells by promoting YAP-mediated ferroptosis. Phytomedicine, 2024. 135: p. 156110.

[10] Wang, L., et al., Advances in targeting tumor microenvironment for immunotherapy. Front Immunol, 2024. 15: p. 1472772.

[11] Wang, W., et al., Identifies microtubule-binding protein CSPP1 as a novel cancer biomarker associated with ferroptosis and tumor microenvironment. Comput Struct Biotechnol J, 2022. 20: p. 3322-3335.

Downloads

Published

05-09-2025

How to Cite

Gao, Y. (2025). The Role of Ferroptosis in Lung Cancer and Its Immunotherapeutic Targeting Strategy. Highlights in Science, Engineering and Technology, 153, 7-11. https://doi.org/10.54097/388s4238