Unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategies
Abstract The success of cancer therapy has been significantly hampered by various mechanisms of therapeutic resistance. Chief among these mechanisms is the presence of clonal heterogeneity within an individual tumor mass. The introduction of the concept of cancer stem cells (CSCs)—a rare and immatur...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | MedComm – Oncology |
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| Online Access: | https://doi.org/10.1002/mog2.70009 |
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| author | Yunhan Tan Siyuan Qin Zhe Zhang Yongen Liu Li Zhou Bowen Li Edouard C. Nice Yuanyuan Zhang Jing Jing |
| author_facet | Yunhan Tan Siyuan Qin Zhe Zhang Yongen Liu Li Zhou Bowen Li Edouard C. Nice Yuanyuan Zhang Jing Jing |
| author_sort | Yunhan Tan |
| collection | DOAJ |
| description | Abstract The success of cancer therapy has been significantly hampered by various mechanisms of therapeutic resistance. Chief among these mechanisms is the presence of clonal heterogeneity within an individual tumor mass. The introduction of the concept of cancer stem cells (CSCs)—a rare and immature subpopulation with tumorigenic potential that contributes to intratumoral heterogeneity—has deepened our understanding of drug resistance. Given the characteristics of CSCs, such as increased drug‐efflux activity, enhanced DNA‐repair capacity, high metabolic plasticity, adaptability to oxidative stress, and/or upregulated detoxifying aldehyde dehydrogenase (ALDH) enzymes, CSCs have been recognized as a theoretical reservoir for resistant diseases. Implicit in this recognition is the possibility that CSC‐targeted therapeutic strategies might offer a breakthrough in overcoming drug resistance in cancer patients. Herein, we summarize the generation of CSCs and our current understanding of the mechanisms underlying CSC‐mediated therapeutic resistance. This extended knowledge has progressively been translated into novel anticancer therapeutic strategies and significantly enriched the available options for combination treatments, all of which are anticipated to improve clinical outcomes for patients experiencing CSC‐related relapse. |
| format | Article |
| id | doaj-art-5f575703db714ecbb80faa998e8475cd |
| institution | DOAJ |
| issn | 2769-6448 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm – Oncology |
| spelling | doaj-art-5f575703db714ecbb80faa998e8475cd2025-08-20T02:40:52ZengWileyMedComm – Oncology2769-64482025-03-0141n/an/a10.1002/mog2.70009Unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategiesYunhan Tan0Siyuan Qin1Zhe Zhang2Yongen Liu3Li Zhou4Bowen Li5Edouard C. Nice6Yuanyuan Zhang7Jing Jing8Department of Biotherapy, Institute of Oxidative Stress Medicine, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital Sichuan University Chengdu People's Republic of ChinaDepartment of Biotherapy, Institute of Oxidative Stress Medicine, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital Sichuan University Chengdu People's Republic of ChinaMOE Joint International Research, Laboratory of Pancreatic Diseases, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital Zhejiang University School of Medicine Hangzhou People's Republic of ChinaState Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology Sichuan University Chengdu Sichuan People's Republic of ChinaKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital Chongqing Medical University Chongqing People's Republic of ChinaDepartment of Biotherapy, Institute of Oxidative Stress Medicine, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital Sichuan University Chengdu People's Republic of ChinaDepartment of Biochemistry and Molecular Biology Monash University, Clayton Victoria AustraliaKey Laboratory of Drug‐Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy Sichuan University Chengdu People's Republic of ChinaFrontiers Medical Center Tianfu Jincheng Laboratory Chengdu People's Republic of ChinaAbstract The success of cancer therapy has been significantly hampered by various mechanisms of therapeutic resistance. Chief among these mechanisms is the presence of clonal heterogeneity within an individual tumor mass. The introduction of the concept of cancer stem cells (CSCs)—a rare and immature subpopulation with tumorigenic potential that contributes to intratumoral heterogeneity—has deepened our understanding of drug resistance. Given the characteristics of CSCs, such as increased drug‐efflux activity, enhanced DNA‐repair capacity, high metabolic plasticity, adaptability to oxidative stress, and/or upregulated detoxifying aldehyde dehydrogenase (ALDH) enzymes, CSCs have been recognized as a theoretical reservoir for resistant diseases. Implicit in this recognition is the possibility that CSC‐targeted therapeutic strategies might offer a breakthrough in overcoming drug resistance in cancer patients. Herein, we summarize the generation of CSCs and our current understanding of the mechanisms underlying CSC‐mediated therapeutic resistance. This extended knowledge has progressively been translated into novel anticancer therapeutic strategies and significantly enriched the available options for combination treatments, all of which are anticipated to improve clinical outcomes for patients experiencing CSC‐related relapse.https://doi.org/10.1002/mog2.70009cancer stem cells (CSCs)combination therapyCSC‐targeted therapydrug resistance |
| spellingShingle | Yunhan Tan Siyuan Qin Zhe Zhang Yongen Liu Li Zhou Bowen Li Edouard C. Nice Yuanyuan Zhang Jing Jing Unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategies MedComm – Oncology cancer stem cells (CSCs) combination therapy CSC‐targeted therapy drug resistance |
| title | Unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategies |
| title_full | Unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategies |
| title_fullStr | Unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategies |
| title_full_unstemmed | Unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategies |
| title_short | Unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategies |
| title_sort | unraveling the underlying mechanisms of cancer stem cells in therapeutic resistance for optimizing treatment strategies |
| topic | cancer stem cells (CSCs) combination therapy CSC‐targeted therapy drug resistance |
| url | https://doi.org/10.1002/mog2.70009 |
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