Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment
Ferroptosis, a distinct regulated cell death process characterized by iron retention and lipid peroxidation, plays a crucial role in the survival of cancer stem cells (CSCs), key contributors to cancer initiation, progression, and recurrence. CSCs exhibit enhanced iron uptake and altered lipid metab...
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KeAi Communications Co., Ltd.
2025-11-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304225001679 |
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| author | Luyao Wang Ye Zhu Chengying Huang Qiuming Pan Junxi Wang Hongrui Li Yudi Huang Guozhong Yi Zhiyong Li Songtao Qi Guanglong Huang Shanqiang Qu |
| author_facet | Luyao Wang Ye Zhu Chengying Huang Qiuming Pan Junxi Wang Hongrui Li Yudi Huang Guozhong Yi Zhiyong Li Songtao Qi Guanglong Huang Shanqiang Qu |
| author_sort | Luyao Wang |
| collection | DOAJ |
| description | Ferroptosis, a distinct regulated cell death process characterized by iron retention and lipid peroxidation, plays a crucial role in the survival of cancer stem cells (CSCs), key contributors to cancer initiation, progression, and recurrence. CSCs exhibit enhanced iron uptake and altered lipid metabolism, allowing them to evade conventional therapies and persist within the cancer microenvironment. Their resilience is linked to low reactive oxygen species levels, aiding survival under oxidative stress. Key regulatory pathways, including the cystine/glutathione axis, significantly modulate CSCs' sensitivity to ferroptosis by maintaining a balance between antioxidant defenses and pro-oxidative stressors. Targeting ferroptosis in CSCs offers promising therapeutic avenues for enhancing treatment efficacy and overcoming resistance. Strategies such as pharmacological inhibition of the SLC7A11 transporter, which reduces cysteine availability and glutathione levels, can potentiate ferroptosis in CSCs. Additionally, inducing dysregulation of iron metabolism or lipid peroxidation can selectively compromise CSCs' survival. Nanoparticle drug delivery systems that increase intracellular iron and reactive oxygen species levels are proving effective in targeting CSCs with minimal impact on normal cells. Ultimately, a comprehensive understanding of the interplay between ferroptosis and CSCs' biology is essential for developing innovative strategies aimed at eradicating these elusive cells, thereby improving cancer treatment outcomes and reducing recurrence rates. |
| format | Article |
| id | doaj-art-be1b16c5ce534c55846da7f5f2dc7b1b |
| institution | Kabale University |
| issn | 2352-3042 |
| language | English |
| publishDate | 2025-11-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj-art-be1b16c5ce534c55846da7f5f2dc7b1b2025-08-24T05:13:17ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-11-0112610167810.1016/j.gendis.2025.101678Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatmentLuyao Wang0Ye Zhu1Chengying Huang2Qiuming Pan3Junxi Wang4Hongrui Li5Yudi Huang6Guozhong Yi7Zhiyong Li8Songtao Qi9Guanglong Huang10Shanqiang Qu11Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; The First Clinical School of Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; The First Clinical School of Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Obstetrics and Gynecology, Baiyun Branch, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510440, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; The First Clinical School of Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; The First Clinical School of Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; The First Clinical School of Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; The First Clinical School of Medicine, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Institute of Brain Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Institute of Brain Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Institute of Brain Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Institute of Brain Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, ChinaDepartment of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Nanfang Glioma Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Institute of Brain Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China; Corresponding author. Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou Dadao Bei Street 1838, Guangzhou, Guangdong 510515, China.Ferroptosis, a distinct regulated cell death process characterized by iron retention and lipid peroxidation, plays a crucial role in the survival of cancer stem cells (CSCs), key contributors to cancer initiation, progression, and recurrence. CSCs exhibit enhanced iron uptake and altered lipid metabolism, allowing them to evade conventional therapies and persist within the cancer microenvironment. Their resilience is linked to low reactive oxygen species levels, aiding survival under oxidative stress. Key regulatory pathways, including the cystine/glutathione axis, significantly modulate CSCs' sensitivity to ferroptosis by maintaining a balance between antioxidant defenses and pro-oxidative stressors. Targeting ferroptosis in CSCs offers promising therapeutic avenues for enhancing treatment efficacy and overcoming resistance. Strategies such as pharmacological inhibition of the SLC7A11 transporter, which reduces cysteine availability and glutathione levels, can potentiate ferroptosis in CSCs. Additionally, inducing dysregulation of iron metabolism or lipid peroxidation can selectively compromise CSCs' survival. Nanoparticle drug delivery systems that increase intracellular iron and reactive oxygen species levels are proving effective in targeting CSCs with minimal impact on normal cells. Ultimately, a comprehensive understanding of the interplay between ferroptosis and CSCs' biology is essential for developing innovative strategies aimed at eradicating these elusive cells, thereby improving cancer treatment outcomes and reducing recurrence rates.http://www.sciencedirect.com/science/article/pii/S2352304225001679Cancer stemcells (CSCs)Cell signalingDrug targetFerroptosisIron metabolism |
| spellingShingle | Luyao Wang Ye Zhu Chengying Huang Qiuming Pan Junxi Wang Hongrui Li Yudi Huang Guozhong Yi Zhiyong Li Songtao Qi Guanglong Huang Shanqiang Qu Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment Genes and Diseases Cancer stemcells (CSCs) Cell signaling Drug target Ferroptosis Iron metabolism |
| title | Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment |
| title_full | Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment |
| title_fullStr | Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment |
| title_full_unstemmed | Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment |
| title_short | Targeting ferroptosis in cancer stem cells: A novel strategy to improve cancer treatment |
| title_sort | targeting ferroptosis in cancer stem cells a novel strategy to improve cancer treatment |
| topic | Cancer stemcells (CSCs) Cell signaling Drug target Ferroptosis Iron metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2352304225001679 |
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