Perspectives on cancer therapy—synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges
Abstract In recent years, synthetic lethality has become an important theme in the field of targeted cancer therapy. Synthetic lethality refers to simultaneous defects in two or more genes leading to cell death, whereas defects in any single gene do not lead to cell death. Taking advantage of the ge...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-04-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02418-8 |
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| author | Shixuan Peng Mengle Long Qisheng Chen Zhijian Yin Chang Zeng Wanyong Zhang Qingyang Wen Xinwen Zhang Weiqi Ke Yongjun Wu |
| author_facet | Shixuan Peng Mengle Long Qisheng Chen Zhijian Yin Chang Zeng Wanyong Zhang Qingyang Wen Xinwen Zhang Weiqi Ke Yongjun Wu |
| author_sort | Shixuan Peng |
| collection | DOAJ |
| description | Abstract In recent years, synthetic lethality has become an important theme in the field of targeted cancer therapy. Synthetic lethality refers to simultaneous defects in two or more genes leading to cell death, whereas defects in any single gene do not lead to cell death. Taking advantage of the genetic vulnerability that exists within cancer cells, it theoretically has no negative impact on healthy cells and has fewer side effects than non-specific chemotherapy. Currently, targeted cancer therapies focus on inhibiting key pathways in cancer. However, it has been found that over-activation of oncogenic-related signaling pathways can also induce cancer cell death, which is a major breakthrough in the new field of targeted therapies. In this review, we summarize the conventional gene targets in synthetic lethality (PARP, ATR, ATM, WEE1, PRMT) and provide an in-depth analysis of their latest potential mechanisms. We explore the impact of over-activation of pathways such as PI3K/AKT, MAPK, and WNT on cancer cell survival, and present the technical challenges of current research. Important theoretical foundations and insights are provided for the application of synthetic lethal strategies in cancer therapy, as well as future research directions. |
| format | Article |
| id | doaj-art-69dc2e1da9444d82b3af3a9c8ac06dca |
| institution | DOAJ |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-69dc2e1da9444d82b3af3a9c8ac06dca2025-08-20T03:18:30ZengNature Publishing GroupCell Death Discovery2058-77162025-04-0111111710.1038/s41420-025-02418-8Perspectives on cancer therapy—synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challengesShixuan Peng0Mengle Long1Qisheng Chen2Zhijian Yin3Chang Zeng4Wanyong Zhang5Qingyang Wen6Xinwen Zhang7Weiqi Ke8Yongjun Wu9Department of Oncology, Graduate Collaborative Training Base of The First People’s Hospital of Xiangtan City, Hengyang Medical School, University of South ChinaDepartment of Oncology, Graduate Collaborative Training Base of The First People’s Hospital of Xiangtan City, Hengyang Medical School, University of South ChinaDepartment of Anesthesiology, The First People’s Hospital of Chenzhou, The Chenzhou Affiliated Hospital, Hengyang Medical School, University of South ChinaDepartment of Oncology, Graduate Collaborative Training Base of The First People’s Hospital of Xiangtan City, Hengyang Medical School, University of South ChinaDepartment of Pathology, Yueyang Central HospitalDepartment of Pathology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and TechnologyDepartment of Oncology, Graduate Collaborative Training Base of The First People’s Hospital of Xiangtan City, Hengyang Medical School, University of South ChinaDepartment of Oncology, Graduate Collaborative Training Base of The First People’s Hospital of Xiangtan City, Hengyang Medical School, University of South ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Shantou University Medical CollegeDepartment of Pathology, Xiangtan Center HospitalAbstract In recent years, synthetic lethality has become an important theme in the field of targeted cancer therapy. Synthetic lethality refers to simultaneous defects in two or more genes leading to cell death, whereas defects in any single gene do not lead to cell death. Taking advantage of the genetic vulnerability that exists within cancer cells, it theoretically has no negative impact on healthy cells and has fewer side effects than non-specific chemotherapy. Currently, targeted cancer therapies focus on inhibiting key pathways in cancer. However, it has been found that over-activation of oncogenic-related signaling pathways can also induce cancer cell death, which is a major breakthrough in the new field of targeted therapies. In this review, we summarize the conventional gene targets in synthetic lethality (PARP, ATR, ATM, WEE1, PRMT) and provide an in-depth analysis of their latest potential mechanisms. We explore the impact of over-activation of pathways such as PI3K/AKT, MAPK, and WNT on cancer cell survival, and present the technical challenges of current research. Important theoretical foundations and insights are provided for the application of synthetic lethal strategies in cancer therapy, as well as future research directions.https://doi.org/10.1038/s41420-025-02418-8 |
| spellingShingle | Shixuan Peng Mengle Long Qisheng Chen Zhijian Yin Chang Zeng Wanyong Zhang Qingyang Wen Xinwen Zhang Weiqi Ke Yongjun Wu Perspectives on cancer therapy—synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges Cell Death Discovery |
| title | Perspectives on cancer therapy—synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges |
| title_full | Perspectives on cancer therapy—synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges |
| title_fullStr | Perspectives on cancer therapy—synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges |
| title_full_unstemmed | Perspectives on cancer therapy—synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges |
| title_short | Perspectives on cancer therapy—synthetic lethal precision medicine strategies, molecular mechanisms, therapeutic targets and current technical challenges |
| title_sort | perspectives on cancer therapy synthetic lethal precision medicine strategies molecular mechanisms therapeutic targets and current technical challenges |
| url | https://doi.org/10.1038/s41420-025-02418-8 |
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