题名 | A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors |
作者 | Zhang, Chao1,2; Guo, Qiang3; Chen, Lifeng4,5; Wu, Zheming2; Yan, Xiao-Jian6; Zou, Chengyang6; Zhang, Qiuxue7; Tan, Jiahong8; Fang, Tian8; Rao, Qunxian9; Li, Yang10; Shen, Shizhen11; Deng, Min2; Wang, Liewei12; Gao, Huanyao12; Yu, Jia12; Li, Hu12; Zhang, Cheng12; Nowsheen, Somaira13; Kloeber, Jake2; Zhao, Fei2; Yin, Ping2; Teng, Chunbo14; Lin, Zhongqiu9; Song, Kun15; Yao, Shuzhong16; Yao, Liangqing17; Wu, Lingying18; Zhang, Yong19; Cheng, Xiaodong10,20; Gao, Qinglei8; Yuan, Jian21,22; Lou, Zhenkun2; Zhang, Jin-San23,24
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发表日期 | 2023-05-10 |
发表期刊 | SIGNAL TRANSDUCTION AND TARGETED THERAPY 影响因子和分区 |
语种 | 英语 |
原始文献类型 | Article |
其他关键词 | HOMOLOGOUS RECOMBINATION-DEFICIENT ; OLAPARIB MAINTENANCE THERAPY ; PARP INHIBITOR OLAPARIB ; OVARIAN-CANCER ; PHASE-II ; REPAIR ; CELLS ; BIOGENESIS ; ATM ; SENSITIVITY |
摘要 | Poly (ADP-ribose) polymerase (PARP) inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination (HR) deficiency. However, many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin. The biomarker responsible for this mechanism remains unclear. Here, we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients. PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage (ATM) signaling-induced pro-apoptotic ribosomal stress, which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage. Therefore, the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin. The gene panel as an independent biomarker was validated by multiple published clinical datasets, as well as by an ovarian cancer organoids library we established. More importantly, its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data. Furthermore, we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines. These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance. Together, our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy. |
资助项目 | Department of Oncology[PEO1/ABT-888];key research and development program of Zhejiang province[2019C03010];National Natural Science Foundation of China[81772787,82072889];CSCO[Y-2019AZZD-0359];National Key Technology Research and Development Program of China[2022YFC2704200,2022YFC2704205]; |
出版者 | SPRINGERNATURE |
ISSN | 2095-9907 |
EISSN | 2059-3635 |
卷号 | 8期号:1 |
DOI | 10.1038/s41392-023-01401-y |
页数 | 17 |
WOS类目 | Biochemistry & Molecular Biology ; Cell Biology |
WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
WOS记录号 | WOS:000992507500001 |
收录类别 | SCIE ; PUBMED ; SCOPUS |
URL | 查看原文 |
Pubmed记录号 | 37160887 |
Scopus记录号 | 2-s2.0-85158997035 |
自科自定义期刊分类 | T3(B)类 |
通讯作者地址 | [Lou, Zhenkun]Department of Oncology,Mayo Clinic,Rochester,55905,United States ; [Gao, Qinglei]Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei,Wuhan,430030,China ; [Cheng, Xiaodong]Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine for Reproductive Health Research,Zhejiang,Hangzhou,310006,China ; [Yuan, Jian]Key Laboratory of Arrhythmias of the Ministry of Education of China,Research Center for Translational Medicine,East Hospital,Tongji University School of Medicine,Shanghai,200120,China ; [Zhang, Jin-San]The Quzhou Affiliated Hospital of Wenzhou Medical University,Quzhou People’s Hospital,Zhejiang,Quzhou,324000,China |
scopus学科分类 | Genetics;Cancer Research |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | https://kms.wmu.edu.cn/handle/3ETUA0LF/180009 |
专题 | 药学院(分析测试中心) 附属第一医院 其他_温州医科大学附属衢州医院 |
通讯作者 | Cheng, Xiaodong; Gao, Qinglei; Yuan, Jian; Lou, Zhenkun; Zhang, Jin-San |
作者单位 | 1.Beijing Institute of Basic Medical Sciences,Beijing,100850,China; 2.Department of Oncology,Mayo Clinic,Rochester,55905,United States; 3.School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 4.Key Laboratory of Endocrine Gland Diseases of Zhejiang Province,Zhejiang Provincial People’s Hospital,Zhejiang,Hangzhou,310014,China; 5.Department of Gynecology,Zhejiang Provincial People’s Hospital,Zhejiang,Hangzhou,310014,China; 6.Department of Gynecology,the First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 7.Wuhan Kingwise Biotechnology Co.,Ltd.,Hubei,Wuhan,430206,China; 8.Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei,Wuhan,430030,China; 9.Department of Gynecological Oncology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangdong,Guangzhou,510120,China; 10.Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine for Reproductive Health Research,Zhejiang,Hangzhou,310006,China; 11.Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases,Zhejiang,Hangzhou,310006,China; 12.Department of Molecular Pharmacology and Experimental Therapeutics,Mayo Clinic,Rochester,55905,United States; 13.Department of Dermatology,University of California San Diego,San Diego,92122,United States; 14.Key Laboratory of Saline-alkali Vegetation Ecology Restoration,Ministry of Education,College of Life Science,Northeast Forestry University,Harbin,150040,China; 15.Division of Gynecology Oncology,Department of Obstetrics and Gynecology,Qilu Hospital,Shandong University,Shandong,Jinan,250012,China; 16.Department of Obstetrics and Gynecology,the First Affiliated Hospital,Sun Yat-Sen University,Guangdong,Guangzhou,510080,China; 17.Department of Gynecologic Oncology,Obstetrics and Gynecology Hospital of Fudan University,Shanghai,200090,China; 18.Department of Gynecologic Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,100021,China; 19.Department of Radiation Oncology,Hubei Cancer Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei,Wuhan,430030,China; 20.Department of Gynecologic Oncology,Women’s Hospital,School of Medicine,Zhejiang University,Zhejiang,Hangzhou,310006,China; 21.Key Laboratory of Arrhythmias of the Ministry of Education of China,Research Center for Translational Medicine,East Hospital,Tongji University School of Medicine,Shanghai,200120,China; 22.Department of Biochemistry and Molecular Biology,Tongji University School of Medicine,Shanghai,200120,China; 23.The Quzhou Affiliated Hospital of Wenzhou Medical University,Quzhou People’s Hospital,Zhejiang,Quzhou,324000,China; 24.Medical Research Center,and Key Laboratory of Interventional Pulmonology of Zhejiang Province,The First Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China |
通讯作者单位 | 温州医科大学附属衢州医院 |
推荐引用方式 GB/T 7714 | Zhang, Chao,Guo, Qiang,Chen, Lifeng,et al. A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2023,8(1). |
APA | Zhang, Chao., Guo, Qiang., Chen, Lifeng., Wu, Zheming., Yan, Xiao-Jian., ... & Zhang, Jin-San. (2023). A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors. SIGNAL TRANSDUCTION AND TARGETED THERAPY, 8(1). |
MLA | Zhang, Chao,et al."A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors".SIGNAL TRANSDUCTION AND TARGETED THERAPY 8.1(2023). |
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