ResearchIn-Press PreviewOncologyTherapeutics
Open Access | 10.1172/jci.insight.177857
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Yin, J. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Chen, J. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Hong, J. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Huang, Y. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Xiao, R. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Liu, S. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Deng, P. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Sun, Y. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Chai, K. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Zeng, X. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by
Chan, J.
in:
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1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by
Guan, P.
in:
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1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Wang, Y. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Wang, P. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Tong, C. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by
Yu, Q.
in:
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1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Xia, X. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by
Ong, C.
in:
JCI
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PubMed
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Google Scholar
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1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by
Teh, B.
in:
JCI
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PubMed
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1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Xiong, Y. in: JCI | PubMed | Google Scholar
1State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
2Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Guangzhou, Singapore
3Department of Oncology, Guangdong Provincial People’s Hospital, Guangzhou, China
4Department of Laboratory Medicine, South China University of Technology, Guangzhou, China
5Lymphoma Genomic Translational Research Laboratory, Cellular and Molecular, National Cancer Centre Singapore, Singapore, Singapore
6Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
7Genome Institute of Singapore, A*STAR, Singapore, Singapore
8Genome Institute of Singapore, STAR, Singapore, Singapore
9Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore
10State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Singapore, Singapore
Find articles by Tan, J. in: JCI | PubMed | Google Scholar
Published June 6, 2024 - More info
Loss of ferroptosis contributes to the development of human cancer, and restoration of ferroptosis has been demonstrated as a potential therapeutic strategy in cancer treatment. However, the mechanisms of how ferroptosis escape contributes to ovarian cancer (OV) development are not well elucidated. Here we show that ferroptosis negative regulation (FNR) signatures correlated with the tumorigenesis of OV and were associated with poor prognosis, suggesting that restoration of ferroptosis represents a potential therapeutic strategy in OV. High throughput drug screening with a kinase inhibitor library identified MEK inhibitors as ferroptosis inducers in OV cells. We further demonstrated that MEK inhibitor resistant OV cells were less vulnerable to trametinib-induced ferroptosis. Mechanistically, mTOR/4EBP1 signaling promoted SLC7A11 protein synthesis, leading to ferroptosis inhibition in MEK inhibitor resistant cells. Dual inhibition of MEK and mTOR/4EBP1 signaling restrained the protein synthesis of SLC7A11 via suppression of the mTOR-4EBP1 activity to reactivate ferroptosis in resistant cells. Together, these findings provide a promising therapeutic option for OV treatment through ferroptosis restoration by the combined inhibition of MEK and mTOR/4EBP1 pathways.