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Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology.
Ji, Shuyi; Feng, Li; Fu, Zile; Wu, Gaohua; Wu, Yingcheng; Lin, Youpei; Lu, Dayun; Song, Yuanli; Cui, Peng; Yang, Zijian; Sang, Chen; Song, Guohe; Cai, Shangli; Li, Yuanchuang; Lin, Hanqing; Zhang, Shu; Wang, Xiaoying; Qiu, Shuangjian; Zhang, Xiaoming; Hua, Guoqiang; Li, Junqiang; Zhou, Jian; Dai, Zhi; Wang, Xiangdong; Ding, Li; Wang, Pei; Gao, Daming; Zhang, Bing; Rodriguez, Henry; Fan, Jia; Clevers, Hans; Zhou, Hu; Sun, Yidi; Gao, Qiang.
Afiliación
  • Ji S; Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai 201508, China.
  • Feng L; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Fu Z; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
  • Wu G; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Wu Y; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Lin Y; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Lu D; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Song Y; Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Cui P; Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • Yang Z; Burning Rock Biotech, Shanghai 201114, China.
  • Sang C; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Song G; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Cai S; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Li Y; Burning Rock Biotech, Shanghai 201114, China.
  • Lin H; D1 Medical Technology, Shanghai 200235, China.
  • Zhang S; D1 Medical Technology, Shanghai 200235, China.
  • Wang X; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Qiu S; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Zhang X; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Hua G; Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
  • Li J; Department of Radiation Oncology, and Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
  • Zhou J; D1 Medical Technology, Shanghai 200235, China.
  • Dai Z; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Wang X; Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
  • Ding L; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Wang P; Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Institute for Clinical Science, Fudan University Shanghai Medical College, Shanghai 200032, China.
  • Gao D; Department of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University, St. Louis, MO 63108, USA.
  • Zhang B; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NewYork, NY 10029, USA.
  • Rodriguez H; State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China.
  • Fan J; Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
  • Clevers H; Office of Cancer Clinical Proteomics Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhou H; Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China.
  • Sun Y; Department of Radiation Oncology, and Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
  • Gao Q; Oncode Institute, Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.
Sci Transl Med ; 15(706): eadg3358, 2023 07 26.
Article en En | MEDLINE | ID: mdl-37494474
ABSTRACT
Organoid models have the potential to recapitulate the biological and pharmacotypic features of parental tumors. Nevertheless, integrative pharmaco-proteogenomics analysis for drug response features and biomarker investigation for precision therapy of patients with liver cancer are still lacking. We established a patient-derived liver cancer organoid biobank (LICOB) that comprehensively represents the histological and molecular characteristics of various liver cancer types as determined by multiomics profiling, including genomic, epigenomic, transcriptomic, and proteomic analysis. Proteogenomic profiling of LICOB identified proliferative and metabolic organoid subtypes linked to patient prognosis. High-throughput drug screening revealed distinct response patterns of each subtype that were associated with specific multiomics signatures. Through integrative analyses of LICOB pharmaco-proteogenomics data, we identified the molecular features associated with drug responses and predicted potential drug combinations for personalized patient treatment. The synergistic inhibition effect of mTOR inhibitor temsirolimus and the multitargeted tyrosine kinase inhibitor lenvatinib was validated in organoids and patient-derived xenografts models. We also provide a user-friendly web portal to help serve the biomedical research community. Our study is a rich resource for investigation of liver cancer biology and pharmacological dependencies and may help enable functional precision medicine.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteogenómica / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteogenómica / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: China