The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index.
Human primary liver cancer–derived organoid cultures for disease modeling and drug screening
Open accessAbstract
Human liver cancer research currently lacks in vitro models that can faithfully recapitulate the pathophysiology of the original tumor. We recently described a novel, near-physiological organoid culture system, wherein primary human healthy liver cells form long-term expanding organoids that retain liver tissue function and genetic stability. Here we extend this culture system to the propagation of primary liver cancer (PLC) organoids from three of the most common PLC subtypes: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC) and combined HCC/CC (CHC) tumors. PLC-derived organoid cultures preserve the histological architecture, gene expression and genomic landscape of the original tumor, allowing for discrimination between different tumor tissues and subtypes, even after long-term expansion in culture in the same medium conditions. Xenograft studies demonstrate that the tumorogenic potential, histological features and metastatic properties of PLC-derived organoids are preserved in vivo. PLC-derived organoids are amenable for biomarker identification and drug-screening testing and led to the identification of the ERK inhibitor SCH772984 as a potential therapeutic agent for primary liver cancer. We thus demonstrate the wide-ranging biomedical utilities of PLC-derived organoid models in furthering the understanding of liver cancer biology and in developing personalized-medicine approaches for the disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A greater degree of divergence may be attributed to intra-tumor spatial heterogeneity and sampling bias: tumors can be spatially diverse, and organoids generated from a specific portion may lack the representativeness of distant regions130,131.”
From Organoids (2022) · cites this paper as [131]
Experimental — accuracy not yet measuredIn the citing paper
“Furthermore, with recent technological advancements (e.g. organoid models and conditionally reprogrammed cell lines), a new generation of cancer cell models is being derived to allow full representation of the histopathological and molecular diversity of tumours (37–42).”
From Cell Model Passports-a hub for clinical, genetic and functional datasets of preclinical cancer models (2019) · cites this paper as [38]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · cited 2×
“Normalised counts were created using DESeq2 [69] and RPKMs using edgeR's 1213 function [edgeR].”
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400 · cited 1×
“6) [73] and the output was 1245 preprocessed for variant calling by marking duplicates with Picard (v1.”
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012) · Fly · doi:10.4161/fly.19695 · Cited by 11,816
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
Analysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587
UniProt: the Universal Protein knowledgebase
Apweiler, R. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh131 · Cited by 7,593
dbSNP: the NCBI database of genetic variation
Sherry, S. T. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.308 · Cited by 7,502
Flagged first, then by citations
Cited by
Sorted by citations
Items 401–500 of 1,001
van Tienderen, G. S., Li, L., Broutier, L., Saito, Y., Inácio, P., Huch, M., Selaru, F. M., van der Laan, L. J. W., & Verstegen, M. M. A. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.02.001 · Cited by 35
Self-citationAdvances and Applications of Brain Organoids
Li, Y., Zeng, P.-M., Wu, J., & Luo, Z. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01065-2 · Cited by 40
“Previous studies have built a complete experimental system for drug screening for cancer using organoid technology [125–127], but the application of organoids in NDDs is more challenging because of the complexity of the origin of neuronal cell types, cell-type specific pathogenesis, and complicated…”
BackgroundShin, J., Chung, H., Kumar, H., Meadows, K., Park, S. S., Chun, J., & Kim, K. (2024) · Bioprinting · doi:10.1016/j.bprint.2024.e00337 · Cited by 35
Raffo‐Romero, A., Ziane-Chaouche, L., Salomé‐Desnoulez, S., Hajjaji, N., Fournier, I., Salzet, M., & Duhamel, M. (2024) · Cell Reports Methods · doi:10.1016/j.crmeth.2024.100792 · Cited by 36
eIF3f promotes tumour malignancy by remodelling fatty acid biosynthesis in hepatocellular carcinoma
Zhou, S., Zhang, L., You, Y., Yu, K., Tie, X., Gao, Y., Chen, Y., Yao, F., Zhang, R., Hao, X., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.02.045 · Cited by 35
Bian, Y., Teper, Y., Griner, L. A. M., Aiken, T. J., Shukla, V., Guha, R., Shinn, P., Xin, H.-W., Pflicke, H., Powers, A. S., et al. (2019) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-18-1011 · Cited by 35
“Recently, both homogenous spheroid models and organoid models have been advanced into drug screening studies in hopes of better targeting these CSC subpopulations to provide more appropriate leads for clinical translation (17, 18).”
BackgroundRegenerative Engineering: Current Applications and Future Perspectives
Goldenberg, D., McLaughlin, C., Koduru, S. V., & Ravnic, D. J. (2021) · Frontiers in Surgery · doi:10.3389/fsurg.2021.731031 · Cited by 37
High-grade serous ovarian carcinoma organoids as models of chromosomal instability
Vias, M., Gavarró, L. M., Sauer, C. M., Sanders, D. A., Piskorz, A., Couturier, D., Ballereau, S. J., Hernando, B., Schneider, M. P., Hall, J. A. M., et al. (2023) · eLife · doi:10.7554/elife.83867 · Cited by 35
“Consistent with studies in ovarian cancer and other tissue types (Lee et al., 2018; Gao et al., 2014; Broutier et al., 2017; Francies et al., 2016) our results confirm the feasibility of using PDOs for testing drug sensitivity in HGSOC.”
ResultSelf-citationHuman-cell-derived organoids as a new ex vivo model for drug assays in oncology
Mebarki, M., Griscelli, A. B., & Bonhomme‐Faivre, L. (2018) · Drug Discovery Today · doi:10.1016/j.drudis.2018.02.003 · Cited by 34
Three-dimensional tumor cell cultures employed in virotherapy research
Kloker, L. D., Yurttas, C., & Lauer, U. M. (2018) · Oncolytic Virotherapy · doi:10.2147/ov.s165479 · Cited by 34
“Until now, human tumoroids have been established successfully from colon cancer, 80,81 prostate 82 and pancreatic tumors, 83 primary liver cancer, 84 and glioblastoma.”
Linden, C. V., & Corbet, C. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.05.016 · Cited by 34
The Organoid Era Permits the Development of New Applications to Study Glioblastoma
Andreatta, F., Beccaceci, G., Fortuna, N., Celotti, M., Felice, D. D., Lorenzoni, M., Foletto, V., Genovesi, S., Rubert, J., & Alaimo, A. (2020) · Cancers · doi:10.3390/cancers12113303 · Cited by 36
Zhao, Y., Zhang, B., Ma, Y., Zhao, F., Chen, J., Wang, B., Jin, H., Zhou, F., Guan, J., Zhao, Q., et al. (2022) · Advanced Science · doi:10.1002/advs.202201539 · Cited by 34
Gao, J., Lan, J., Liao, H., Yang, F., Qiu, P., Jin, F., Wang, S., Shen, L., Chao, T., Zhang, C., et al. (2023) · BMC Cancer · doi:10.1186/s12885-023-11434-9 · Cited by 37
“…preclinical model to evaluate therapeutic responses in vitro, involving lung cancer [70–72], colorectal cancer [29, 73–75], breast cancer [76, 77], ovarian cancer [78, 79], pancreatic cancer [80, 81], liver cancer [82, 83], neuroendocrine neoplasms [53], oesophageal cancer and gastric cancer.”
BackgroundImaging 3D cell cultures with optical microscopy
Hsieh, H.-C., Han, Q., Brenes, D., Bishop, K. W., Wang, R., Wang, Y., Poudel, C., Glaser, A. K., Freedman, B., Vaughan, J. C., et al. (2025) · Nature Methods · doi:10.1038/s41592-025-02647-w · Cited by 38
Organoids for Advanced Therapeutics and Disease Models
Kim, S., Cho, A., Min, S., Kim, S., & Cho, S. (2018) · Advanced Therapeutics · doi:10.1002/adtp.201800087 · Cited by 33
Karolak, A. M., Poonja, S., & Rejniak, K. A. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007214 · Cited by 33
Parker, R. N., Cairns, D. M., Wu, W. A., Jordan, K. E., Guo, C., Huang, W., Martín‐Moldes, Z., & Kaplan, D. L. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202000266 · Cited by 33
Organoids in Translational Oncology
Tatullo, M., Marrelli, B., Benincasa, C., Aiello, E., Im, M., Zavan, B., Ballini, A., Vito, D. D., & Spagnuolo, G. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9092774 · Cited by 36
“…Primary Liver Cancer Chemotherapy SCH772984 inhibited the activation of the ERK protein and demonstrated to play a crucial role in the tumorigenesis Broutier et al. (2017) Cultured tumoroids in mice Human Primary Liver Cancer Chemotherapy SCH772984 reduced tumor growth in mice treated with this…”
BackgroundResultInfluentialProtocol for generation of lung adenocarcinoma organoids from clinical samples
Li, Z., Yu, L., Chen, D., Meng, Z., Chen, W., & Huang, W. (2020) · STAR Protocols · doi:10.1016/j.xpro.2020.100239 · Cited by 33
Rao, S., Hossain, T., & Mahmoudi, T. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.02.024 · Cited by 34
Emerging liver organoid platforms and technologies
Lam, D. T. U. H., Dan, Y. Y., Chan, Y.-S., & Ng, H. (2021) · Cell Regeneration · doi:10.1186/s13619-021-00089-1 · Cited by 36
Lim, J. J., Hooi, L., Dan, Y. Y., Bonney, G. K., Zhou, L., Chow, P. K. H., Chee, C. E., Toh, T. B., & Chow, E. K. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02436-9 · Cited by 33
“Cells were subsequently counted and seeded into cell culture flasks in DMEM/F12 medium (Biowest) supplemented with defined growth factors [38, 41] for culture and further experiments.”
MethodLiver organoids: an in vitro 3D model for liver cancer study
Dong, R., Zhang, B., & Zhang, X. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00890-8 · Cited by 33
“[7, 8], brain [9], kidney [10], lung [11], prostate [12], colon [13], pancreas [14, 15], liver [16], and some cancer organoids, such as brain tumors [17], pancreatic cancer [18], and PLC [19].”
BackgroundInfluentialIntegration of organoids in peptide drug discovery: Rise of the high‐throughput screening
Zhang, S., Shen, J., Wang, X., Sun, X., Wu, Y., Zhang, M., Wang, R., & Hu, K. (2023) · Open Research (University of Surrey) · doi:10.1002/viw.20230010 · Cited by 33
On-chip modeling of tumor evolution: Advances, challenges and opportunities
Li, C., Holman, J. B., Shi, Z., Qiu, B., & Ding, W. (2023) · Materials Today Bio · doi:10.1016/j.mtbio.2023.100724 · Cited by 33
Design Approaches for Generating Organ Constructs
Xia, Y. F., & Belmonte, J. C. I. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.05.016 · Cited by 32
Use of preclinical models for malignant pleural mesothelioma
Shamseddin, M., Obacz, J., Garnett, M. J., Rintoul, R. C., Francies, H. E., & Marciniak, S. J. (2021) · Thorax · doi:10.1136/thoraxjnl-2020-216602 · Cited by 30
Self-citationChallenges for the Applications of Human Pluripotent Stem Cell-Derived Liver Organoids
Chang, M., Bogacheva, M. S., & Lou, Y. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.748576 · Cited by 36
Patient‐Derived Upper Tract Urothelial Carcinoma Organoids as a Platform for Drug Screening
Li, Z., Xu, H., Gong, Y., Chen, W., Zhan, Y., Yu, L., Sun, Y., Li, A., He, S., Guan, B., et al. (2021) · Advanced Science · doi:10.1002/advs.202103999 · Cited by 32
Precision oncology using ex vivo technology: a step towards individualised cancer care?
Williams, S. T., Wells, G., Conroy, S., Gagg, H., Allen, R. J., Rominiyi, O., Helleday, T., Hullock, K., Pennington, C. E. W., Rantala, J., et al. (2022) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2022.32 · Cited by 35
Development of glioblastoma organoids and their applications in personalized therapy
Xu, C., Yuan, X., Hou, P., Li, Z., Wang, C., Fang, C., & Tan, Y. (2023) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2023.0061 · Cited by 38
A decade of liver organoids: Advances in disease modeling
Liu, Y., Sheng, J.-Y., Yang, C.-F., Ding, J., & Chan, Y.-S. (2023) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2022.0428 · Cited by 30
“The landmark study by Broutier et al.(35) demonstrated the potential of the organoid platform to achieve that”
BackgroundInfluentialOpportunities and challenges to engineer 3D models of tumor-adaptive immune interactions
Visalakshan, R. M., Lowrey, M. K., Sousa, M. G. C., Helms, H. R., Samiea, A., Schutt, C. E., Moreau, J. M., & Bertassoni, L. E. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1162905 · Cited by 32
“In addition, PDTOs using adult stem cells have been used to establish organoids for a myriad of cancer types including but not limited to lung (90), colon (89), liver (91), pancreas (92, 93), prostate (94, 95), kidney (96), and breast (97) cancers.”
MethodExpansion of airway basal epithelial cells from primary human non‐small cell lung cancer tumors
Hynds, R. E., Aïssa, A. B., Gowers, K. H. C., Watkins, T. B. K., Bosshard‐Carter, L., Rowan, A., Veeriah, S., Wilson, G. A., Quezada, S. A., Swanton, C., et al. (2018) · International Journal of Cancer · doi:10.1002/ijc.31383 · Cited by 31
Katsumi, T., Guicciardi, M. E., Azad, A. I., Bronk, S. F., Krishnan, A., & Gores, G. J. (2019) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00250.2019 · Cited by 32
The Progress and Clinical Application of Breast Cancer Organoids
Yu, J. S., & Huang, W. (2020) · International Journal of Stem Cells · doi:10.15283/ijsc20082 · Cited by 32
Fan, Z., Gao, Y., Zhang, W., Yang, G., Liu, P., Xu, L., Wang, J., Yan, Z., Han, H., Liu, R., et al. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.01.085 · Cited by 31
3D Hepatic Organoid-Based Advancements in LIVER Tissue Engineering
Panwar, A., Das, P., & Tan, L. P. (2021) · Bioengineering · doi:10.3390/bioengineering8110185 · Cited by 32
“The given studies were in accordance with the drug sensitivity of tumors present in patients [57].”
ResultEstablishment of a patient-derived organoid model and living biobank for nasopharyngeal carcinoma
Wang, X., Xia, T., Tang, H., Liu, X., Han, R., Zou, X., Zhao, Y.-T., Chen, M., & Li, G. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-1076 · Cited by 31
“Previous studies had found that several cytokines, including Wnt3a, R-spondin-1 (Rspo-1), EGF, Y27632, Noggin, and FGF2, were important for organoid generation (21-24).”
BackgroundIdentification of PRMT5 as a therapeutic target in cholangiocarcinoma
Elurbide, J., Colyn, L., Latasa, M. U., Uriarte, I., Mariani, S., López-Pascual, A., Valbuena-Goiricelaya, E., Castelló-Uribe, B., Arnes‐Benito, R., Adán-Villaescusa, E., et al. (2024) · Gut · doi:10.1136/gutjnl-2024-332998 · Cited by 32
“38 We observed that treatment with GSK3326595 potently reduced tumouroid growth, with the presence of smaller organoids filled with dying (figure 4).”
Self-citationLi, P., Huang, M., Ma, Y., Zhang, Y., & Shi, C. (2024) · Cancer Cell International · doi:10.1186/s12935-024-03628-3 · Cited by 32
Suppression of Hepatocellular Carcinoma by Mycophenolic Acid in Experimental Models and in Patients
Chen, K., Sheng, J., Ma, B., Cao, W., Hernanda, P. Y., Liu, J., Boor, P. P. C., Tjon, A. S. W., Felczak, K., Sprengers, D., et al. (2019) · Transplantation · doi:10.1097/tp.0000000000002647 · Cited by 29
“The organoid technology (culturing “mini-organ” in three dimension) has endowed the possibility of establishing stable cultures from primary tumors, including for liver tumors.(27,28,34) Our data support that MPA has potent inhibitory effects on HCC growth in vitro.”
BackgroundSpheres of Influence: Insights into Salmonella Pathogenesis from Intestinal Organoids
Verma, S., Senger, S., Cherayil, B. J., & Faherty, C. S. (2020) · Microorganisms · doi:10.3390/microorganisms8040504 · Cited by 30
Xu, F., Tong, M., Tong, C. S. W., Chan, B. K. C., Chu, H. Y., Wong, T. L., Fong, J. H. C., Cheung, M. S. H., Mak, K. H.-M., Pardeshi, L. A., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-1017 · Cited by 30
“Ifenprodil treatment enhances the efficacy of sorafenib in HCC patient-derived organoids and xenograft models Human primary liver cancer–derived organoid culture models the pathophysiology of a growing tumor in vivo (42).”
BackgroundLee, J. H., Kim, H., Lee, S. H., Ku, J., Chun, J. W., Seo, H., Kim, S., Paik, W. H., Ryu, J. K., Lee, S. K., et al. (2021) · Gut and Liver · doi:10.5009/gnl210166 · Cited by 34
Zheng, Q., Zhang, B., Li, C., & Zhang, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.850732 · Cited by 31
Słomka, A., Wang, B., Mocan, T., Horhat, A., Willms, A. G., Schmidt‐Wolf, I. G. H., Strassburg, C. P., Gonzalez-Carmona, M. A., Kornek, M., & Kornek, M. (2022) · Theranostics · doi:10.7150/thno.73400 · Cited by 30
“92% of variants as seen in patient’s tissue were retained in the corresponding early tumouroid cultures (< 2 months), and > 80% after months of additional expansion [150].”
BackgroundOptofluidic imaging meets deep learning: from merging to emerging
Siu, D. M. D., Lee, K. C. M., Chung, B. M. F., Wong, J. S. J., Zheng, G., & Tsia, K. K. (2023) · Lab on a Chip · doi:10.1039/d2lc00813k · Cited by 30
Organoids as preclinical models of human disease: progress and applications
Chen, B., Du, C., Wang, M., Guo, J., & Liu, X. (2024) · Medical Review · doi:10.1515/mr-2023-0047 · Cited by 31
Toward reproducible tumor organoid culture: focusing on primary liver cancer
Guo, L., Li, C., & Gong, W. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1290504 · Cited by 34
“As previously discussed, Tüysüz et al. (83) demonstrated the successful serum-free generation of human organoids from healthy and diseased intestines and livers using stabilized Wnt3a.”
BackgroundMethodInfluentialYang, R., Kwan, W., Du, Y., Yan, R., Zang, L., Li, C., Zhu, Z., Cheong, I. H., Kozlakidis, Z., & Yu, Y. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.217106 · Cited by 29
Preclinical Models of Hepatocellular Carcinoma: Current Utility, Limitations, and Challenges
Cigliano, A., Liao, W., Deiana, G. A., Rizzo, D., Chen, X., & Calvisi, D. F. (2024) · Biomedicines · doi:10.3390/biomedicines12071624 · Cited by 32
“Human liver tumoroids could be sourced from surgical specimens, suitable for early-stage HCC that could be cured by surgical resection [45].”
BackgroundMethodInfluentialClinical Implementation of Precision Medicine in Gastric Cancer
Jeon, J., & Cheong, J. (2019) · Journal of the Korean Gastric Cancer Association · doi:10.5230/jgc.2019.19.e25 · Cited by 31
“PDOs generated from various cancer types retain the genetic and histologic features of the original tumor, including their microarchitecture and physiology [61-69].”
BackgroundIn Vitro Modeling of Non-Solid Tumors: How Far Can Tissue Engineering Go?
Trujillo, S. C., Ferrer, G. G., & Ribelles, J. L. G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165747 · Cited by 34
“Scaffold-free models such as spheroids and organoids have achieved great in vitro results [15,19].”
BackgroundHuman cell transformation by combined lineage conversion and oncogene expression
Sahu, B., Pihlajamaa, P., Zhang, K., Palin, K., Ahonen, S., Cervera, A., Ristimaki, A. P., Aaltonen, L. A., Hautaniemi, S., & Taipale, J. (2021) · Oncogene · doi:10.1038/s41388-021-01940-0 · Cited by 31
“Other recently developed experimental approaches for mechanistic studies of human cancers have used for example primary human epithelial cells [30] and primary liver cancer-derived organoids [63].”
BackgroundSukei, T., Palma, E., & Urbani, L. (2021) · Cancers · doi:10.3390/cancers13215586 · Cited by 29
Studying Kidney Diseases Using Organoid Models
Liu, M., Cardilla, A., Ngeow, J. Y. Y., Gong, X., & Xia, Y. F. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.845401 · Cited by 31
“, 2016), liver tumour (Broutier et al., 2017), and ovarian tumour (Kopper et al.”
BackgroundMetabolic Studies in Organoids: Current Applications, Opportunities and Challenges
Richiardone, E., den Bossche, V. V., & Corbet, C. (2022) · Organoids · doi:10.3390/organoids1010008 · Cited by 29
“Major recent advances in 3D culture technology have led to the development of patient-derived tumor organoids (PDTO) for a variety of cancer types, including breast [107], bladder [108], colorectal [109], head and neck [110], liver [111], pancreatic [112], gastrointestinal [113], glioblastoma [114], retinoblastoma [11…”
BackgroundUsing Biosensors to Study Organoids, Spheroids and Organs-on-a-Chip: A Mechanobiology Perspective
Yousafzai, M. S., & Hammer, J. A. (2023) · Biosensors · doi:10.3390/bios13100905 · Cited by 30
“…along with adult stem cells, have been used extensively to create organoid cultures for various tissues including intestine [56,125], stomach [130,131], kidney [132,133], lung [134,135], liver [136,137], pancreas [138,139], breast [140,141], brain [142,143], and optic cup [129,144] (Figure 5).”
BackgroundOrganoid Models of Cancer Explode with Possibilities
Muthuswamy, S. K. (2018) · Cell stem cell · doi:10.1016/j.stem.2018.02.010 · Cited by 29
Identification of the best housekeeping gene for RT-qPCR analysis of human pancreatic organoids
Cherubini, A., Rusconi, F., & Lazzari, L. (2021) · PLoS ONE · doi:10.1371/journal.pone.0260902 · Cited by 26
“The main reasons for their considerable use are their plasticity and multiple applications, including as new models to study specific diseases [2], in regenerative medicine [3] and the screening of new drugs [4].”
BackgroundBao, D., Wang, L., Zhou, X., Yang, S., He, K., & Xu, M. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1133090 · Cited by 29
“In recent years, an increasing variety of cancer organoid have been successfully established, including but not limited to liver and bile duct (Broutier et al., 2017), bladder (Lee et al.”
BackgroundKalla, J., Pfneissl, J., Mair, T., Tran, L., & Egger, G. (2024) · Cellular Oncology · doi:10.1007/s13402-024-00960-8 · Cited by 31
Takada, K., Aizawa, Y., Sano, D., Okuda, R., Sekine, K., Ueno, Y., Yamanaka, S., Aoyama, J., Sato, K., Kuwahara, T., et al. (2020) · International Journal of Cancer · doi:10.1002/ijc.33315 · Cited by 28
“Organoid viability assays were conducted with some modification of previous report.(16) Organoids were dissociated by enzymatic dissociation before being resuspended in 50 μL of complete medium (14 000 organoids) and plated into 96-well cell-culture plate, after coating each well with GFR Matrigel.”
MethodGao, M., Harper, M. M., Lin, M., Qasem, S. A., Patel, R. A., Mardini, S. H., Gabr, M. M., Cavnar, M. J., Pandalai, P. K., & Kim, J. (2020) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2020.11.009 · Cited by 29
“Although there are reports utilizing different methods to manually scale the size of PDOs before drug testing[18, 34], this method can only be applied to an abundant volume of PDOs, which occurs at later passages.”
MethodOrganoid biobanks as a new tool for pre-clinical validation of candidate drug efficacy and safety.
Botti, G., Bonito, M. D., & Cantile, M. (2021) · PubMed Central · Cited by 27
Perspective: Extending the Utility of Three-Dimensional Organoids by Tissue Clearing Technologies
Susaki, E. A., & Takasato, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.679226 · Cited by 26
“Furthermore, the use of a waterabsorbing polymer for Expansion Microscopy (ExM) enables high-resolution imaging with a general microscopy setup (Chen et al., 2015; Ku et al., 2016).”
BackgroundMethodMiyabayashi, K., Nakagawa, H., & Koike, K. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.682872 · Cited by 28
Güney, T. G., Herranz, A. M., Mumby, S. E., Dunlop, I. E., & Adcock, I. M. (2021) · iScience · doi:10.1016/j.isci.2021.103061 · Cited by 31
Ek, F., Blom, K., Selvin, T., Rudfeldt, J., Andersson, C. R., Senkowski, W., Bréchot, C., Nygren, P., Larsson, R. L., Jarvius, M., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-12519-4 · Cited by 27
Human lung organoid: Models for respiratory biology and diseases
Yang, W., Li, Y., Shi, F., & Liu, H. (2022) · Developmental Biology · doi:10.1016/j.ydbio.2022.12.001 · Cited by 26
Liver Organoids as an In Vitro Model to Study Primary Liver Cancer
Siervi, S. D., & Turato, C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054529 · Cited by 30
“Recent studies have shown that tumour-derived organoids are capable of retaining the morphological characteristics and biomarkers of the original tumour tissue while also preserving the patient-specific gene expression profile, even when cultivated for extended periods [23,62].”
BackgroundInfluentialWang, T., Tang, Y., Pan, W., Yan, B., Hao, Y., Zeng, Y., Chen, Z., Lan, J., Zhao, S., Deng, C., et al. (2023) · Diseases of the Colon & Rectum · doi:10.1097/dcr.0000000000002511 · Cited by 28
Developing Liver Microphysiological Systems for Biomedical Applications
Wang, J., Wu, X., Zhao, J., Ren, H., & Zhao, Y. (2024) · Advanced Healthcare Materials · doi:10.1002/adhm.202302217 · Cited by 27
Giron‐Michel, J., Padelli, M., Oberlin, E., Guénou, H., & Duclos‐Vallée, J. (2025) · BioDrugs · doi:10.1007/s40259-024-00702-0 · Cited by 31
“This could be explained in part by the fact that CSCs are consistently maintained in PDOs even after long-term expansion in culture [80, 81].”
InfluentialZhu, Z., Cheng, Y., Liu, X., Ding, W., Liu, J., Ling, Z., & Wu, L. (2025) · Cell Transplantation · doi:10.1177/09636897241303271 · Cited by 31
Eisenstein, M. S. (2018) · Nature Methods · doi:10.1038/nmeth.4538 · Cited by 27
Nguyen, R., Bae, S. D. W., Zhou, G., Read, S. A., Ahlenstiel, G., George, J., & Qiao, L. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188350 · Cited by 27
Trends in the development of human stem cell-based non-animal drug testing models
Lee, S.-J., & Lee, H. (2020) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2020.24.6.441 · Cited by 28
The promise of human organoids in the digestive system
Funata, M., Nio, Y., Erion, D. M., Thompson, W. L., & Takebe, T. (2020) · Cell Death and Differentiation · doi:10.1038/s41418-020-00661-3 · Cited by 28
Ultrastructural analysis of breast cancer patient-derived organoids
Signati, L., Allevi, R., Piccotti, F., Albasini, S., Villani, L., Sevieri, M., Bonizzi, A., Corsi, F., & Mazzucchelli, S. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02135-z · Cited by 28
Tumor organoids for cancer research and personalized medicine
Yang, H., Wang, Y., Wang, P., Zhang, N., & Wang, P. (2021) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2021.0335 · Cited by 29
In vitro models for head and neck cancer: Current status and future perspective
Moya‐Garcia, C. R., Okuyama, H., Sadeghi, N., Li, J., Tabrizian, M., & Li‐Jessen, N. Y. K. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.960340 · Cited by 28
“Frontiers in Oncology 02 incorporated into in vitro models, such as breast (14), lung (15), and liver (16) cancers.”
BackgroundGao, Z., Liu, X., Zhao, H., Xia, S., Liu, W., Bai, H., Lv, F., Zheng, X., Huang, Y., Gu, Q., et al. (2023) · Science China Chemistry · doi:10.1007/s11426-022-1472-6 · Cited by 27
Hallmark discoveries in the biology of Wilms tumour
Perotti, D., Williams, R. D., Wegert, J., Brzezinski, J. J., Maschietto, M. C., Ciceri, S., Gisselsson, D., Gadd, S., Walz, A. L., Furtwängler, R., et al. (2023) · Nature Reviews Urology · doi:10.1038/s41585-023-00824-0 · Cited by 29
“Protocols have been developed to culture organoids from a wide spectrum of different adult tumours, including colon 219 , breast 220 , ovarian 221 , pancreas 222 and liver 223 .”
Salas‐Silva, S., Kim, Y., Kim, T. H., Kim, M., Seo, D., Choi, J., Factor, V. M., Seo, H. R., Song, Y., Choi, G. S., et al. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122360 · Cited by 28
Castven, D., Becker, D., Czauderna, C., Wilhelm, D., Andersen, J. B., Strand, S., Hartmann, M., Heilmann‐Heimbach, S., Roth, W., Hartmann, N., et al. (2018) · International Journal of Cancer · doi:10.1002/ijc.32026 · Cited by 27
“A recent study extended the organoid culture system for PLC and derived organoids from HCC, CCA and mixed HCC/CCA and demonstrated that PLC organoids faithfully recapitulated the molecular profile of the original tumors.(31) Further, only few studies exploited the potential of PDx as well as PDCL as a model for liver…”
ResultHuman assembloids recapitulate periportal liver tissue in vitro
Yuan, L., Dawka, S., Kim, Y., Liebert, A., Rost, F., Arnes‐Benito, R., Baenke, F., Götz, C., Tsang, D., Schuhmann, A., et al. (2025) · Nature · doi:10.1038/s41586-025-09884-1 · Cited by 31
“To explore this, we analysed expression profiles from human liver cancer organoids 35 and mouse partial hepatectomy 27 and compared them to those for human healthy and cancer tissues (Supplementary Data 1 and Methods).”
InfluentialSelf-citationEmerging trends in modeling human liver disease in vitro
Underhill, G. H., & Khetani, S. R. (2019) · APL Bioengineering · doi:10.1063/1.5119090 · Cited by 26
Epigenetic Regulation of Cell-Fate Changes That Determine Adult Liver Regeneration After Injury
Aloia, L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.643055 · Cited by 25
Liver Organoids: Updates on Disease Modeling and Biomedical Applications
Caiazza, C., Parisi, S., & Caiazzo, M. (2021) · Biology · doi:10.3390/biology10090835 · Cited by 28
Willemse, J., van der Laan, L. J. W., de Jonge, J., & Verstegen, M. M. A. (2022) · Bioengineering · doi:10.3390/bioengineering9030110 · Cited by 26
Self-citationYu, Y., Zhu, Y.-J., Xiao, Z., Chen, Y., Chang, X., Liu, Y., Tang, Q., & Zhang, H. (2022) · Biomarker Research · doi:10.1186/s40364-022-00421-0 · Cited by 27
“The establishment of long-term BE PDOs was achieved in the condition with 20% R-spondin-1 conditioned medium and 50% Wnt-3A conditioned medium, and the addition of PGE2 [58].”
BackgroundInfluentialSun, H., Yang, H., & Mao, Y. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1150151 · Cited by 28
“Furthermore, it is more important that HCC PDOs are highly concordant with original tumor biopsies in terms of growth pattern, degree of differentiation, expression of HCCspecific markers, genomic alterations, and ability to form tumors in xenograft models (Broutier et al., 2017; Nuciforo et al., 2018).”
BackgroundCheng, J., Xie, W., Chen, Y., Sun, Y., Gong, L., Wang, H., Li, C., & Zhang, Y. (2024) · Drug Resistance Updates · doi:10.1016/j.drup.2024.101056 · Cited by 26
Precision oncology in liver cancer
Sullivan, K. M., Kenerson, H. L., Pillarisetty, V. G., Riehle, K. J., & Yeung, R. S. W. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.06.14 · Cited by 26
Wang, L., Koui, Y., Kanegae, K., Kido, T., Tamura-Nakano, M., Yabe, S., Tai, K., Nakajima, Y., Kusuhara, H., Sakai, Y., et al. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122621 · Cited by 25
Applications of Organoids in Advancing Drug Discovery and Development
Gopallawa, I., Gupta, C., Jawa, R., Cyril, A., Jawa, V., Chirmule, N. B., & Gujar, V. (2024) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2024.06.016 · Cited by 29
Liver organoids: updates on generation strategies and biomedical applications
Liu, S., Cheng, C., Zhu, L., Zhao, T., Wang, Z., Yi, X., Yan, F., Wang, X., Li, C., Cui, T., et al. (2024) · Stem Cell Research & Therapy · doi:10.1186/s13287-024-03865-3 · Cited by 29
“[ 138 ] W i t h 129 c a n c e r d r u g s , g e n e r a t i n g 3 , 483 c e ll s u r v i v a l d a t a p o i n t s l a y t h e f o u n d a t i o n f o r i n - d e p t h s t u d i e s o f p a n - e ff e c t i v e d r u g s , a s w e ll a s f o r f u n c t i o n a l p e r s o n a l - i z e d o n c o…”
BackgroundMethodInfluential
Metadata
- Authors
- Broutier, L., Mastrogiovanni, G., Verstegen, M. M., Francies, H. E., Gavarró, L. M., Bradshaw, C. R., Allen, G. E., Arnes-Benito, R., Sidorova, O., Gaspersz, M. P., Georgakopoulos, N., Koo, B.-K., Dietmann, S., Davies, S. E., Praseedom, R. K., Lieshout, R., IJzermans, J. N. M., Wigmore, S. J., Saeb-Parsy, K., Garnett, M. J., van der Laan, L. J., & Huch, M.
- Affiliations
- University of Cambridge (GB)
- Wellcome/MRC Cambridge Stem Cell Institute (GB)
- Erasmus MC (NL)
- Wellcome Sanger Institute (GB)
- Cambridge University Hospitals NHS Foundation Trust (GB)
- Edinburgh Royal Infirmary (GB)
- Corresponding author
- Huch, Meritxell
- ORCID
- Broutier, Laura
- Mastrogiovanni, Gianmarco
- Verstegen, Monique MA
- Gavarró, Lena Morrill
- Bradshaw, Charles R
- Allen, George E
- Sidorova, Olga
- Gaspersz, Marcia P
- Georgakopoulos, Nikitas
- Koo, Bon-Kyoung
- Dietmann, Sabine
- Davies, Susan E
- Praseedom, Raaj K
- Lieshout, Ruby
- IJzermans, Jan N M
- Wigmore, Stephen J
- Garnett, Mathew J
- Huch, Meritxell
- Venue
- Nature Medicine
- Published
- 2017-11-13
- Volume
- 23
- Issue
- 12
- Pages
- 1424-1435
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC5722201
- OpenAlex
- W2771057425
- Cited by
- 1,471
- References
- 74
- Citations by year
- 2026: 151 · 2025: 163 · 2024: 203 · 2023: 182 · 2022: 204 · 2021: 243 · 2020: 151 · 2019: 99 · 2018: 73 · 2017: 2
- FWCI
- 39.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- HAL (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo
- Funders
- Wellcome Trust (104151/Z/14/Z, C44943/A22536, 104151, 102696)
- Cancer Research UK (102696, C44943/A22536, 22536)
- University of Cambridge
- European Commission (656193, 608180)
- National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/R001162/1)
- ZonMw
- Cambridge University Hospitals
- National Centre for the Replacement Refinement and Reduction of Animals in Research (NC/R001162/1)
- Stand Up To Cancer (SU2C-AACRDT1213)
- Horizon 2020 Framework Programme (MSCA-IF-2014)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- primary liver cancer, tumor organoids, hepatocellular carcinoma, cholangiocarcinoma, organoid culture, disease modeling, drug screening, xenografts, metastasis, biomarker discovery, ERK inhibitor, SCH772984, personalized medicine
- MeSH terms
- Animals, Antineoplastic Agents, Bile Duct Neoplasms, Drug Screening Assays, Antitumor, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Organoids, Tumor Cells, Cultured, Gene Expression Regulation, Neoplastic, Mice, SCID, Mice, Inbred NOD, Cholangiocarcinoma, Xenograft Model Antitumor Assays, Cell Proliferation, Mice, Precision Medicine, Transcriptome, Primary Cell Culture
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review