Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening
Open accessAbstract
Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalised medicine. Here, we report lung cancer organoids and normal bronchial organoids established from patient tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2-mutant organoid to olaparib, an EGFR-mutant organoid to erlotinib, and an EGFR-mutant/MET-amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting patient-specific drug responses through in vitro patient-specific drug trials.
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Organoid cultures are easier to manipulate and study biologically in depth than animal models.
“Organoid cultures are more accessible for manipulation and in-depth biological studies14 than animal models.”
From Organoids (2022) · cites this paper as [14]
The introduction (page unavailable) says patient-derived xenograft animal models are costly, slow to establish and limited for high-throughput studies, while organoids take less time to establish. That supports greater practical accessibility, but the paper does not establish that organoids are easier to manipulate or better suited to in-depth biological studies than animal models. (LLM, conf=0.82)
Experimental — accuracy not yet measuredOrganoid cultures are fundamentally based on accumulated knowledge of developmental biology, where soluble cues are presented to cells in a spatiotemporally controlled manner.
“Organoid cultures are fundamentally based on our accumulated knowledge of developmental biology14, where soluble cues are presented to cells in a spatiotemporally controlled manner”
From Organoids (2022) · cites this paper as [14]
The Discussion says the authors drew on prior lung-organoid culture work to add Wnt3a, Noggin and A83-01 to promote lung development. This supports using developmental cues in organoid culture, but neither the Discussion nor the Methods describes presenting soluble cues with spatial and temporal control. (LLM, conf=0.85)
Experimental — accuracy not yet measured
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“35 Cisplatin, for example, has been found to be less effective in patient-derived organoids (PDOs) generated from non-small cell lung cancer (NSCLC) tissues than from cell lines, highlighting the ability of patient-derived material to provide important information on potential resistance mechanisms.”
BackgroundLung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week
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“, 2020), lung cancer (Kim et al., 2019), breast cancer (Campaner et al.”
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- Authors
- Kim, M., Mun, H., Sung, C. O., Cho, E. J., Jeon, H.-J., Chun, S.-M., Jung, D. J., Shin, T. H., Jeong, G. S., Kim, D. K., Choi, E. K., Jeong, S.-Y., Taylor, A. M., Jain, S., Meyerson, M., & Jang, S. J.
- Affiliations
- Asan Medical Center (KR)
- Harvard University (US)
- Corresponding author
- Jang, Se Jin
- ORCID
- Venue
- Nature Communications
- Published
- 2019-09-05
- Volume
- 10
- Issue
- 1
- Pages
- 3991-3991
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6728380
- OpenAlex
- W2971872568
- Cited by
- 812
- References
- 74
- Citations by year
- 2026: 91 · 2025: 131 · 2024: 150 · 2023: 126 · 2022: 111 · 2021: 134 · 2020: 68 · 2019: 1
- FWCI
- 33.28
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Research Foundation
- Ministry of Trade, Industry and Energy (10067407, 10067796)
- National Research Foundation of Korea
- Asan Institute for Life Sciences, Asan Medical Center
- National Cancer Institute (R35CA197568)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
- Keywords
- lung cancer organoids, patient-derived organoids, in vitro tumor model, therapeutic screening, personalized medicine, drug response prediction, BRCA2 mutation, olaparib, EGFR mutation, erlotinib, MET amplification, crizotinib, histological subtypes
- MeSH terms
- Animals, Drug Screening Assays, Antitumor, Humans, Lung Neoplasms, Organoids, Mice, SCID, Mice, Inbred NOD, Xenograft Model Antitumor Assays, Genomics, Mice, Early Detection of Cancer, Precision Medicine, B7-H1 Antigen
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