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• Could 3D models of cancer enhance drug screening?
• Precision Oncology: Who, How, What, When, and When Not?

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         headline:Clinical translation of patient-derived tumour organoids- bottlenecks and strategies
         description:Multiple three-dimensional (3D) tumour organoid models assisted by multi-omics and Artificial Intelligence (AI) have contributed greatly to preclinical drug development and precision medicine. The intrinsic ability to maintain genetic and phenotypic heterogeneity of tumours allows for the reconciliation of shortcomings in traditional cancer models. While their utility in preclinical studies have been well established, little progress has been made in translational research and clinical trials. In this review, we identify the major bottlenecks preventing patient-derived tumour organoids (PDTOs) from being used in clinical setting. Unsuitable methods of tissue acquisition, disparities in establishment rates and a lengthy timeline are the limiting factors for use of PDTOs in clinical application. Potential strategies to overcome this include liquid biopsies via circulating tumour cells (CTCs), an automated organoid platform and optical metabolic imaging (OMI). These proposed solutions accelerate and optimize the workflow of a clinical organoid drug screening. As such, PDTOs have the potential for potential applications in clinical oncology to improve patient outcomes. If remarkable progress is made, cancer patients can finally benefit from this revolutionary technology.
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      description:Multiple three-dimensional (3D) tumour organoid models assisted by multi-omics and Artificial Intelligence (AI) have contributed greatly to preclinical drug development and precision medicine. The intrinsic ability to maintain genetic and phenotypic heterogeneity of tumours allows for the reconciliation of shortcomings in traditional cancer models. While their utility in preclinical studies have been well established, little progress has been made in translational research and clinical trials. In this review, we identify the major bottlenecks preventing patient-derived tumour organoids (PDTOs) from being used in clinical setting. Unsuitable methods of tissue acquisition, disparities in establishment rates and a lengthy timeline are the limiting factors for use of PDTOs in clinical application. Potential strategies to overcome this include liquid biopsies via circulating tumour cells (CTCs), an automated organoid platform and optical metabolic imaging (OMI). These proposed solutions accelerate and optimize the workflow of a clinical organoid drug screening. As such, PDTOs have the potential for potential applications in clinical oncology to improve patient outcomes. If remarkable progress is made, cancer patients can finally benefit from this revolutionary technology.
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      affiliation:
            name:Yong Loo Lin School of Medicine, National University of Singapore
            address:
               name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:National University of Singapore
            address:
               name:Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
      name:Glenn K. Bonney
      affiliation:
            name:National University Hospital
            address:
               name:Department of Surgery, National University Hospital, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:Yong Loo Lin School of Medicine, National University of Singapore
            address:
               name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
      name:Wei-Peng Yong
      affiliation:
            name:Cancer Science Institute of Singapore, National University of Singapore
            address:
               name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:National University Hospital, National University Health System
            address:
               name:Department of Haematology-Oncology, National University Hospital, National University Health System, Singapore, Singapore
               type:PostalAddress
            type:Organization
      name:Edward Kai-Hua Chow
      affiliation:
            name:Cancer Science Institute of Singapore, National University of Singapore
            address:
               name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:Yong Loo Lin School of Medicine, National University of Singapore
            address:
               name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:National University of Singapore
            address:
               name:Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
      name:Eliza Li Shan Fong
      affiliation:
            name:Cancer Science Institute of Singapore, National University of Singapore
            address:
               name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:National University of Singapore
            address:
               name:Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
      name:Lingzhi Wang
      url:http://orcid.org/0000-0001-5585-5426
      affiliation:
            name:Cancer Science Institute of Singapore, National University of Singapore
            address:
               name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:Yong Loo Lin School of Medicine, National University of Singapore
            address:
               name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:National University of Singapore
            address:
               name:Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Boon-Cher Goh
      affiliation:
            name:Cancer Science Institute of Singapore, National University of Singapore
            address:
               name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:Yong Loo Lin School of Medicine, National University of Singapore
            address:
               name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:National University of Singapore
            address:
               name:Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
               type:PostalAddress
            type:Organization
            name:National University Hospital, National University Health System
            address:
               name:Department of Haematology-Oncology, National University Hospital, National University Health System, Singapore, Singapore
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
      name:Hangzhou Cancer Institute, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Hangzhou, China
      name:Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, China
      name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
      name:Department of Surgery, National University Hospital, Singapore, Singapore
      name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
      name:Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
      name:Department of Surgery, National University Hospital, Singapore, Singapore
      name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
      name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
      name:Department of Haematology-Oncology, National University Hospital, National University Health System, Singapore, Singapore
      name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
      name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
      name:Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
      name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
      name:Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore
      name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
      name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
      name:Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
      name:Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
      name:NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
      name:Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
      name:Department of Haematology-Oncology, National University Hospital, National University Health System, Singapore, Singapore

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