Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology-Reference-Cited by-同舟云学术

Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology

Published:2023-07-26 Issue:706 Volume:15 Page:
ISSN:1946-6234
Container-title:Science Translational Medicine
language:en
Short-container-title:Sci. Transl. Med.

Author:

Ji Shuyi¹²^ORCID,Feng Li³^ORCID,Fu Zile²^ORCID,Wu Gaohua²^ORCID,Wu Yingcheng²^ORCID,Lin Youpei²^ORCID,Lu Dayun⁴,Song Yuanli⁴,Cui Peng⁵^ORCID,Yang Zijian²,Sang Chen²^ORCID,Song Guohe²,Cai Shangli⁵,Li Yuanchuang⁶,Lin Hanqing⁶^ORCID,Zhang Shu²,Wang Xiaoying²,Qiu Shuangjian²,Zhang Xiaoming⁷^ORCID,Hua Guoqiang⁸,Li Junqiang⁶^ORCID,Zhou Jian²⁹,Dai Zhi²,Wang Xiangdong¹⁰^ORCID,Ding Li¹¹,Wang Pei¹²,Gao Daming¹³,Zhang Bing¹⁴^ORCID,Rodriguez Henry¹⁵,Fan Jia²⁸,Clevers Hans¹⁶^ORCID,Zhou Hu²⁴¹⁷^ORCID,Sun Yidi³^ORCID,Gao Qiang¹²⁹¹⁸^ORCID

Affiliation:

1. Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai 201508, China.

2. 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.

3. Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.

4. Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

5. Burning Rock Biotech, Shanghai 201114, China.

6. D1 Medical Technology, Shanghai 200235, China.

7. Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.

8. Department of Radiation Oncology, and Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.

9. Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

10. Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital Institute for Clinical Science, Fudan University Shanghai Medical College, Shanghai 200032, China.

11. Department of Medicine, McDonnell Genome Institute, Siteman Cancer Center, Washington University, St. Louis, MO 63108, USA.

12. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NewYork, NY 10029, USA.

13. 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.

14. Lester and Sue Smith Breast Center, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.

15. Office of Cancer Clinical Proteomics Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

16. Oncode Institute, Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, Netherlands.

17. Shanghai Institute of Materia Medica–University of Ottawa Joint Research Center in Systems and Personalized Pharmacology, Shanghai 201203, China.

18. State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai 200433, China.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Link

https://www.science.org/doi/pdf/10.1126/scitranslmed.adg3358

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