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A ribosomal gene panel predicting a novel synthetic lethality in non-BRCAness tumors.
Zhang, Chao; Guo, Qiang; Chen, Lifeng; Wu, Zheming; Yan, Xiao-Jian; Zou, Chengyang; Zhang, Qiuxue; Tan, Jiahong; Fang, Tian; Rao, Qunxian; Li, Yang; Shen, Shizhen; Deng, Min; Wang, Liewei; Gao, Huanyao; Yu, Jia; Li, Hu; Zhang, Cheng; Nowsheen, Somaira; Kloeber, Jake; Zhao, Fei; Yin, Ping; Teng, Chunbo; Lin, Zhongqiu; Song, Kun; Yao, Shuzhong; Yao, Liangqing; Wu, Lingying; Zhang, Yong; Cheng, Xiaodong; Gao, Qinglei; Yuan, Jian; Lou, Zhenkun; Zhang, Jin-San.
Afiliación
  • Zhang C; Beijing Institute of Basic Medical Sciences, 100850, Beijing, China.
  • Guo Q; Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
  • Chen L; School of Pharmaceutical Sciences, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China.
  • Wu Z; Key Laboratory of Endocrine Gland Diseases of Zhejiang Province, Zhejiang Provincial People's Hospital, 310014, Hangzhou, Zhejiang, China.
  • Yan XJ; Department of Gynecology, Zhejiang Provincial People's Hospital, 310014, Hangzhou, Zhejiang, China.
  • Zou C; Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
  • Zhang Q; Department of Gynecology, the First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China.
  • Tan J; Department of Gynecology, the First Affiliated Hospital of Wenzhou Medical University, 325000, Wenzhou, Zhejiang, China.
  • Fang T; Wuhan Kingwise Biotechnology Co., Ltd., 430206, Wuhan, Hubei, China.
  • Rao Q; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
  • Li Y; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
  • Shen S; Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120, Guangzhou, Guangdong, China.
  • Deng M; Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine for Reproductive Health Research, 310006, Hangzhou, Zhejiang, China.
  • Wang L; Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, 310006, Hangzhou, Zhejiang, China.
  • Gao H; Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
  • Yu J; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
  • Li H; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
  • Zhang C; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
  • Nowsheen S; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
  • Kloeber J; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA.
  • Zhao F; Department of Dermatology, University of California San Diego, San Diego, CA, 92122, USA.
  • Yin P; Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
  • Teng C; Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
  • Lin Z; Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA.
  • Song K; Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, 150040, Harbin, China.
  • Yao S; Department of Gynecological Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 510120, Guangzhou, Guangdong, China.
  • Yao L; Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, 250012, Jinan, Shandong, China.
  • Wu L; Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-Sen University, 510080, Guangzhou, Guangdong, China.
  • Zhang Y; Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital of Fudan University, 200090, Shanghai, China.
  • Cheng X; 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, 100021, Beijing, China.
  • Gao Q; Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
  • Yuan J; Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine for Reproductive Health Research, 310006, Hangzhou, Zhejiang, China. chengxd@zju.edu.cn.
  • Lou Z; Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, 310006, Hangzhou, Zhejiang, China. chengxd@zju.edu.cn.
  • Zhang JS; Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China. qingleigao@hotmail.com.
Signal Transduct Target Ther ; 8(1): 183, 2023 05 10.
Article en En | MEDLINE | ID: mdl-37160887
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Cisplatino Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: Signal Transduct Target Ther Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Cisplatino Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Female / Humans Idioma: En Revista: Signal Transduct Target Ther Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido