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Human patient derived organoids: an emerging precision medicine model for gastrointestinal cancer research
Sicheng Yan1,2, Yuxuan He1,2, Yuehong Zhu1,2
1Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, The Affiliated Central Hospital of Huzhou University, Huzhou, China.
Abstract:
Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality with a poor prognosis. It is one of the leading causes of cancer-related deaths worldwide. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. As a novel preclinical model, tumor patient-derived organoids (PDOs), can be established from patients' tumor tissue and cultured in the laboratory in 3D architectures. This 3D model can not only highly simulate and preserve key biological characteristics of the source tumor tissue in vitro but also reproduce the in vivo tumor microenvironment through co-culture. Our review provided an overview of the different in vitro models in current tumor research, the derivation of cells in PDO models, and the application of PDO model technology in gastrointestinal cancers, particularly the applications in combination with CRISPR/Cas9 gene editing technology, tumor microenvironment simulation, drug screening, drug development, and personalized medicine. It also elucidates the ethical status quo of organoid research and the current challenges encountered in clinical research, and offers a forward-looking assessment of the potential paths for clinical organoid research advancement.
Insights
Patient-derived organoids (PDOs) offer a promising 3D model for gastrointestinal cancer research. These advanced models improve drug screening and personalized medicine development, addressing limitations of current therapies.
Area of Science:
- Oncology
- Biotechnology
- Cancer Research
Background:
- Gastrointestinal cancers represent a significant global health burden, causing substantial mortality.
- Current preclinical models often fail to adequately predict treatment efficacy, hindering therapeutic development.
- Patient-derived organoids (PDOs) are emerging as a superior in vitro model for cancer research.
Purpose of the Study:
- To review the application of PDO technology in gastrointestinal cancer research.
- To explore PDOs' potential in drug screening, development, and personalized medicine.
- To discuss ethical considerations and future directions for organoid research.
Main Methods:
- Review of existing literature on in vitro cancer models and PDO technology.
- Analysis of PDO derivation, culture, and application in gastrointestinal cancers.
- Examination of PDO integration with CRISPR/Cas9, tumor microenvironment simulation, and drug development.
Main Results:
- PDOs accurately mimic patient tumor biology and the tumor microenvironment in vitro.
- PDOs facilitate advanced drug screening, development, and personalized treatment strategies.
- Integration with gene editing technologies enhances PDO utility for mechanistic studies.
Conclusions:
- PDOs represent a significant advancement over traditional models for gastrointestinal cancer research.
- Further development of PDO technology holds great promise for improving cancer therapy and patient outcomes.
- Addressing ethical and clinical challenges is crucial for the widespread adoption of PDOs in healthcare.
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