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Next-generation cancer organoids.
Literature Information
| DOI | 10.1038/s41563-021-01057-5 |
|---|---|
| PMID | 34385685 |
| Journal | Nature materials |
| Impact Factor | 38.5 |
| JCR Quartile | Q1 |
| Publication Year | 2022 |
| Times Cited | 208 |
| Keywords | cancer organoids, personalized medicine, biological heterogeneity, culture techniques, standardization |
| Literature Type | Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review |
| ISSN | 1476-1122 |
| Pages | 143-159 |
| Issue | 21(2) |
| Authors | Bauer L LeSavage, Riley A Suhar, Nicolas Broguiere, Matthias P Lutolf, Sarah C Heilshorn |
TL;DR
This research highlights the transformative role of organotypic models in understanding cancer heterogeneity and advancing personalized medicine, specifically emphasizing the need for standardized protocols in cancer organoid culture due to current inconsistencies in tissue processing and culture conditions. By addressing these challenges, the study aims to enhance the reproducibility and reliability of organoid systems, ultimately facilitating more effective patient care and translational research.
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cancer organoids · personalized medicine · biological heterogeneity · culture techniques · standardization
Abstract
Organotypic models of patient-specific tumours are revolutionizing our understanding of cancer heterogeneity and its implications for personalized medicine. These advancements are, in part, attributed to the ability of organoid models to stably preserve genetic, proteomic, morphological and pharmacotypic features of the parent tumour in vitro, while also offering unprecedented genomic and environmental manipulation. Despite recent innovations in organoid protocols, current techniques for cancer organoid culture are inherently uncontrolled and irreproducible, owing to several non-standardized facets including cancer tissue sources and subsequent processing, medium formulations, and animal-derived three-dimensional matrices. Given the potential for cancer organoids to accurately recapitulate the intra- and intertumoral biological heterogeneity associated with patient-specific cancers, eliminating the undesirable technical variability accompanying cancer organoid culture is necessary to establish reproducible platforms that accelerate translatable insights into patient care. Here we describe the current challenges and recent multidisciplinary advancements and opportunities for standardizing next-generation cancer organoid systems.
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Primary Questions Addressed
- What specific advancements have been made in the protocols for culturing next-generation cancer organoids?
- How do next-generation cancer organoids differ from traditional organoid models in terms of their ability to mimic tumor heterogeneity?
- What role do genomic and environmental manipulations play in enhancing the efficacy of cancer organoids for personalized medicine?
- What are the most significant challenges currently faced in standardizing cancer organoid culture techniques?
- How can interdisciplinary approaches contribute to improving the reproducibility and reliability of cancer organoid systems?
Key Findings
Background and Objectives
The research addresses the challenges associated with cancer heterogeneity and the limitations of current cancer organoid culture techniques. The authors emphasize the importance of developing standardized next-generation cancer organoids that can accurately model the biological diversity of tumors, which is crucial for advancing personalized medicine.
Main Methods/Materials/Experimental Design
The review discusses various aspects of organoid culture, including:
- Tumor Tissue Sourcing: Techniques for obtaining cancer tissue from primary tumors, metastatic lesions, and circulating tumor cells.
- Tissue Processing: Different methods for preparing tissue samples for organoid culture, such as complete dissociation into single cells or mechanical mincing of tissue fragments.
- Culture Medium: The formulation of organoid culture media, highlighting the need for patient-specific components and the challenges posed by the use of animal-derived serum.
- Extracellular Matrix (ECM): The importance of using engineered matrices that can replicate the properties of the tumor ECM for better modeling of cancer biology.
Key Results and Findings
- Cancer organoids derived from patient tissues maintain significant genetic, phenotypic, and therapeutic response heterogeneity, which reflects the original tumor.
- Studies indicate that organoid cultures can be derived from a variety of cancer types with success rates exceeding 70%, which is significantly higher than traditional cancer cell lines.
- The review identifies that current organoid culture techniques suffer from variability due to non-standardized tissue sources, processing methods, and medium formulations.
Main Conclusions/Significance/Innovation
The authors conclude that standardizing cancer organoid culture methods is critical for improving reproducibility and ensuring that these models can effectively represent the complexity of human tumors. The review emphasizes the need for interdisciplinary collaboration to refine these techniques and accelerate the translation of organoid technologies into clinical practice.
Limitations and Future Directions
- Limitations: The efficiency of organoid derivation is still low for many cancer types, and existing models often lack long-term coculture capabilities with other tumor microenvironment (TME) cell types.
- Future Directions: The authors suggest enhancing the standardization of organoid culture protocols, improving the engineering of ECMs, and developing better medium formulations that accurately mimic the in vivo environment. The integration of microfabrication technologies and advances in genetic manipulation techniques are also recommended to improve organoid modeling and drug testing capabilities.
Summary Table
| Aspect | Current Challenges | Future Opportunities |
|---|---|---|
| Tumor Tissue Sourcing | Limited diversity and representation | Multi-region sampling and liquid biopsies |
| Tissue Processing | Non-standardized methods leading to variability | Improved protocols for consistent tissue handling |
| Culture Medium | Dependency on animal-derived components | Development of fully synthetic and patient-specific media |
| Extracellular Matrix (ECM) | Use of poorly defined animal-derived matrices | Engineered matrices with tunable properties |
This comprehensive review highlights the transformative potential of next-generation cancer organoids in modeling tumor heterogeneity and advancing personalized cancer therapies.
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Literatures Citing This Work
- Modeling Metastatic Colonization in a Decellularized Organ Scaffold-Based Perfusion Bioreactor. - Maria Rafaeva;Edward R Horton;Adina R D Jensen;Chris D Madsen;Raphael Reuten;Oliver Willacy;Christian B Brøchner;Thomas H Jensen;Kamilla Westarp Zornhagen;Marina Crespo;Dina S Grønseth;Sebastian R Nielsen;Manja Idorn;Per Thor Straten;Kristoffer Rohrberg;Iben Spanggaard;Martin Højgaard;Ulrik Lassen;Janine T Erler;Alejandro E Mayorca-Guiliani - Advanced healthcare materials (2022)
- Drug Repositioning Based on the Reversal of Gene Expression Signatures Identifies TOP2A as a Therapeutic Target for Rectal Cancer. - Robson Francisco Carvalho;Luisa Matos do Canto;Sarah Santiloni Cury;Torben Frøstrup Hansen;Lars Henrik Jensen;Silvia Regina Rogatto - Cancers (2021)
- Contemporary Molecular Analyses of Malignant Tumors for Precision Treatment and the Implication in Oral Squamous Cell Carcinoma. - Julia Yu Fong Chang;Chih-Huang Tseng;Pei Hsuan Lu;Yi-Ping Wang - Journal of personalized medicine (2021)
- Technologies to Assess Drug Response and Heterogeneity in Patient-Derived Cancer Organoids. - Melissa C Skala;Dustin A Deming;Jeremy D Kratz - Annual review of biomedical engineering (2022)
- Patient-Derived Tumor Organoids: New Progress and Opportunities to Facilitate Precision Cancer Immunotherapy. - Ji Wang;Chao Chen;Lu Wang;Mingjun Xie;Xinyang Ge;Sufan Wu;Yong He;Xiaozhou Mou;Chenyang Ye;Yi Sun - Frontiers in oncology (2022)
- Organoids as Model Systems to Investigate Circadian Clock-Related Diseases and Treatments. - Suengwon Lee;Christian I Hong - Frontiers in genetics (2022)
- Patient-Derived Bladder Cancer Organoid Models in Tumor Biology and Drug Testing: A Systematic Review. - Benjamin Medle;Gottfrid Sjödahl;Pontus Eriksson;Fredrik Liedberg;Mattias Höglund;Carina Bernardo - Cancers (2022)
- The Patient-Derived Cancer Organoids: Promises and Challenges as Platforms for Cancer Discovery. - JuneSung Bae;Yun Sik Choi;Gunsik Cho;Se Jin Jang - Cancers (2022)
- Trends in Tissue Bioprinting, Cell-Laden Bioink Formulation, and Cell Tracking. - Paula Vázquez-Aristizabal;Govindaraj Perumal;Clara García-Astrain;Luis M Liz-Marzán;Ander Izeta - ACS omega (2022)
- 3D Interfacial and Spatiotemporal Regulation of Human Neuroepithelial Organoids. - Chunling Tang;Xinhui Wang;Mirko D'Urso;Cas van der Putten;Nicholas A Kurniawan - Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2022)
... (198 more literatures)
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