Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies
Open accessAbstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second most frequent cause of cancer-related mortality worldwide. The multikinase inhibitor sorafenib is the only treatment option for advanced HCC. Due to tumor heterogeneity, its efficacy greatly varies between patients and is limited due to adverse effects and drug resistance. Current in vitro models fail to recapitulate key features of HCCs. We report the generation of long-term organoid cultures from tumor needle biopsies of HCC patients with various etiologies and tumor stages. HCC organoids retain the morphology as well as the expression pattern of HCC tumor markers and preserve the genetic heterogeneity of the originating tumors. In a proof-of-principle study, we show that liver cancer organoids can be used to test sensitivity to sorafenib. In conclusion, organoid models can be derived from needle biopsies of liver cancers and provide a tool for developing tailored therapies.
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Tumor organoids can be screened to select effective drugs from structurally similar candidates and to investigate synergic effects of drug combinations.
“Tumor organoids can be screened to select effective drugs from structurally similar candidates153 and investigate the synergic effects of different drugs for combination therapy154.”
From Organoids (2022) · cites this paper as [154]
The Results section ('HCC and CCC Organoids Display Variable Sensitivity to Sorafenib'; page not provided) shows that tumor organoids can be tested for drug sensitivity. It tested different concentrations of one drug, sorafenib, not structurally similar candidates from which to select an effective drug. The combination-therapy clause is attached to citation 154, not this source. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDrug screening with organoids can provide connections between genetic mutations and drug responses.
“Since organoids can maintain the genomic profile of the parent tissue158, drug screening can be used to provide connections between genetic mutations and drug responses37,154,159.”
From Organoids (2022) · cites this paper as [154]
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BackgroundDisease modelling in human organoids
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Self-citationTumor organoids: applications in cancer modeling and potentials in precision medicine
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“According to one previous study, liver cancer organoids derived from needle biopsy tissues faithfully model the histopathological features of matched patient tumors even after long-term culture for up to 1 year [84], including the growth pattern, differentiation grade, and the expression”
BackgroundMethodApplication of Cancer Organoid Model for Drug Screening and Personalized Therapy
Kondo, J., & Inoue, M. (2019) · Cells · doi:10.3390/cells8050470 · Cited by 224 · see citing works
“We and oth s have reported the establi hment and use of organoid cultures via the CTOS method in multiple types of cancers, including colorectal [30,86–90], lung [91], urothelial [92–96], liver [97], h ad and neck [98], and uterine [99–101] cancers.”
MethodMechano-modulatory synthetic niches for liver organoid derivation
Sorrentino, G., Rezakhani, S., Yildiz, E., Nuciforo, S., Heim, M. H., Lutolf, M. P., & Schoonjans, K. (2020) · Nature Communications · doi:10.1038/s41467-020-17161-0 · Cited by 224 · see citing works
Self-citationThorel, L., Perréard, M., Florent, R., Divoux, J., Coffy, S., Vincent, A., Gaggioli, C., Guasch, G., Gidrol, X., Weiswald, L., et al. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01272-5 · Cited by 228 · see citing works
A Pharmacogenomic Landscape in Human Liver Cancers
Qiu, Z., Li, H., Zhang, Z., Zhu, Z., He, S., Wang, X., Wang, P., Qin, J., Zhuang, L., Wang, W., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.07.001 · Cited by 202 · see citing works
“Compared to generating HCC orgnaoids (Broutier et al., 2017; Nuciforo et al., 2018), LIMORE provided a relatively higher efficiency (50% vs ~20%).”
BackgroundEmerging organoid models: leaping forward in cancer research
Fan, H., Demirci, U., & Chen, P. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0832-4 · Cited by 199 · see citing works
“The PDTOs displayed a distinct dose-dependent response to the sorafenib treatment in the different patients, which implied the potential value of PDTO models to predict patient-specific drug sensitivities to the targeted drugs [11].”
BackgroundOrganoid models of gastrointestinal cancers in basic and translational research
Lau, H. C.-H., Kranenburg, O., Xiao, H., & Yu, J. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0255-2 · Cited by 195 · see citing works
Applications of organoids for cancer biology and precision medicine
Lo, Y.-H., Karlsson, K., & Kuo, C. J. (2020) · Nature Cancer · doi:10.1038/s43018-020-0102-y · Cited by 182 · see citing works
Zhou, Z., Cong, L., & Cong, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.762184 · Cited by 181 · see citing works
“Numerous PDOs have been established from tissues derived from patients’ tumors, including colon (9), liver (25), gastric (26), lung (27), bladder (28), breast (29), and pancreatic cancers (30, 31) and head and neck squamous cell carcinoma (32).”
BackgroundExploring the promising potential of induced pluripotent stem cells in cancer research and therapy
Chehelgerdi, M., Dehkordi, F. B., Chehelgerdi, M., Kabiri, H., Salehian-Dehkordi, H., Abdolvand, M. A., Salmanizadeh, S., Rashidi, M., Niazmand, A., Ahmadi, S., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01873-0 · Cited by 184 · see citing works
Tumor heterogeneity: preclinical models, emerging technologies, and future applications
Proietto, M., Crippa, M., Damiani, C., Pasquale, V., Sacco, E., Vanoni, M., & Gilardi, M. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1164535 · Cited by 180 · see citing works
“, breast cancer (70), liver cancer (71, 72), gastric cancer (73), colorectal cancer (74), prostate cancer (75), and pancreatic cancer (76–78).”
BackgroundIntegrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages
Ng, C. K. Y., Dazert, E., Boldanova, T., Coto-Llerena, M., Nuciforo, S., Ercan, C., Suslov, A., Meier, M.-A., Bock, T., Schmidt, A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29960-8 · Cited by 165 · see citing works
Self-citationSomatic cell-derived organoids as prototypes of human epithelial tissues and diseases
Fujii, M., & Sato, T. (2020) · Nature Materials · doi:10.1038/s41563-020-0754-0 · Cited by 165 · see citing works
Organoids to model liver disease
Nuciforo, S., & Heim, M. H. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2020.100198 · Cited by 164 · see citing works
Self-citationPatient-derived xenografts and organoids model therapy response in prostate cancer
Karkampouna, S., Manna, F. L., Benjak, A., Kiener, M., Menna, M. D., Zoni, E., Grosjean, J., Klima, I., Garofoli, A., Bolis, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21300-6 · Cited by 164 · see citing works
Self-citationOrganoid cultures for cancer modeling
Yan, H. H. N., Chan, A., Lai, F. P.-L., & Leung, S. Y. (2023) · Cell stem cell · doi:10.1016/j.stem.2023.05.012 · Cited by 163 · see citing works
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Three-dimensional bio-printing of primary human hepatocellular carcinoma for personalized medicine
Xie, F., Sun, L., Pang, Y., Xu, G., Jin, B., Xu, H., Lu, X., Xu, Y., Du, S., Wang, Y., et al. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2020.120416 · Cited by 147 · see citing works
Organoids in gastrointestinal diseases: From experimental models to clinical translation
Günther, C., Winner, B., Neurath, M. F., & Stappenbeck, T. S. (2022) · Gut · doi:10.1136/gutjnl-2021-326560 · Cited by 145 · see citing works
Organoid based personalized medicine: from bench to bedside
Li, Y., Tang, P., Cai, S., Peng, J., & Hua, G. (2020) · Cell Regeneration · doi:10.1186/s13619-020-00059-z · Cited by 138 · see citing works
Pharmaco-proteogenomic characterization of liver cancer organoids for precision oncology
Ji, S., Li, F., Fu, Z., Wu, G., Wu, Y. C., Lin, Y., Lu, D., Song, Y., Cui, P., Yang, Z., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adg3358 · Cited by 141 · see citing works
Patient-Derived Cancer Organoids as Predictors of Treatment Response
Verduin, M., Hoeben, A., Ruysscher, D. D., & Vooijs, M. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.641980 · Cited by 133 · see citing works
“Matched normal liver tissue organoids were also developed by others, providing opportunities to test normal tissue toxicity (32).”
BackgroundResearch Progress, Challenges, and Breakthroughs of Organoids as Disease Models
Huang, Y., Huang, Z., Tang, Z., Chen, Y., Huang, M., Liu, H., Huang, W., Ye, Q., & Jia, B. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.740574 · Cited by 128 · see citing works
“, 2020), liver cancer (Nuciforo et al., 2018), prostate cancer (Puca et al.”
BackgroundZou, F., Tan, J., Liu, T., Liu, B., Tang, Y., Zhang, H., & Li, J. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.01.021 · Cited by 116 · see citing works
“The procedureswere developed by following previous procedureswith minor modifications.(29,43) Briefly, tumor tissues derived from needle biopsies were mechanically dissociated into small pieces using needles and embedded inMatrigel (matrix basementmembrane growth factor reduced, Corning #354230, Corning, Corning, NY,…”
MethodCurrent concepts in tumour-derived organoids
Porter, R. J., Murray, G. I., & McLean, M. H. (2020) · British Journal of Cancer · doi:10.1038/s41416-020-0993-5 · Cited by 114 · see citing works
3D and organoid culture in research: physiology, hereditary genetic diseases and cancer
Suarez-Martinez, E., Suazo-Sanchez, I., Celis-Romero, M., & Carnero, A. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00775-w · Cited by 118 · see citing works
“predicting patient-specific drug sensitivity to targeted drugs [214].”
BackgroundWang, S., Wang, Y., Xun, X., Zhang, C., Xiao, X., Cheng, Q., Hu, S., Li, Z., & Zhu, J. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-1523-2 · Cited by 112 · see citing works
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“Patient-derived CCA organoids were established from resected tissue specimens [11, 23–25] and from needle biopsies [26, 27].”
BackgroundLiver organoid as a 3D in vitro model for drug validation and toxicity assessment
Brooks, A., Liang, X., Zhang, Y., Zhao, C., Roberts, M. S., Wang, H., Zhang, L., & Crawford, D. H. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105608 · Cited by 108 · see citing works
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Dadgar, N., Gonzalez-Suarez, A. M., Fattahi, P., Hou, X., Weroha, J. S., Gaspar-Maia, A., Stybayeva, G., & Revzin, A. (2020) · Microsystems & Nanoengineering · doi:10.1038/s41378-020-00201-6 · Cited by 99 · see citing works
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Zou, Z., Lin, Z., Wu, C., Tan, J., Zhang, J., Peng, Y., Zhang, K., Li, J., Wu, M., & Zhang, Y. (2023) · Advanced Science · doi:10.1002/advs.202302640 · Cited by 102 · see citing works
Mimicking tumor hypoxia and tumor-immune interactions employing three-dimensional in vitro models
Bhattacharya, S., Calar, K., & de la Puente, P. (2020) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-020-01583-1 · Cited by 100 · see citing works
Ding, R., Chen, P., Rajendran, B. K., Lyu, X., Wang, H., Bao, J., Zeng, J., Hao, W., Sun, H., Wong, A. H., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23379-3 · Cited by 96 · see citing works
Microfluidic Organoids-on-a-Chip: Quantum Leap in Cancer Research
Düzağaç, F., Saorin, G., Memeo, L., Canzonieri, V., & Rizzolio, F. (2021) · Cancers · doi:10.3390/cancers13040737 · Cited by 94 · see citing works
“As an example, for breast cancer-specific organoids, the epithelial growth factor receptor (EGFR) ligand EGF to promote cell proliferation, the bone morphogenetic protein (BMP) inhibitor Noggin for cellular expansion, and LGR4/5 (leucine-rich repeat-containing Gprotein-coupled receptor 4/5) ligand R-spondin, which act…”
BackgroundMethodInfluentialEvolution of the Experimental Models of Cholangiocarcinoma
Massa, A., Varamo, C., Vita, F., Tavolari, S., Neia, C. P., Brandi, G., Rizzo, A., Cavalloni, G., & Aglietta, M. (2020) · Cancers · doi:10.3390/cancers12082308 · Cited by 95 · see citing works
Kim, S. K., Kim, Y. H., Park, S., & Cho, S. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.03.002 · Cited by 92 · see citing works
Clinical translation of patient-derived tumour organoids- bottlenecks and strategies
Foo, M. A., You, M., Chan, S. L., Sethi, G., Bonney, G. K., Yong, W. P., Chow, E. K., Fong, E. L. S., Wang, L., & Goh, B.-C. (2022) · Biomarker Research · doi:10.1186/s40364-022-00356-6 · Cited by 94 · see citing works
“Hepatocellular Carcinoma 26% (10/38) [39] 100% (13/17) [40]”
Genetics of Hepatocellular Carcinoma: Approaches to Explore Molecular Diversity
Caruso, S., O’Brien, D. R., Cleary, S. P., Roberts, L. R., & Zucman‐Rossi, J. (2020) · Hepatology · doi:10.1002/hep.31394 · Cited by 92 · see citing works
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A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments
Zhang, Y., Hu, Q., Pei, Y., Luo, H., Wang, Z., Xu, X., Zhang, Q. H., Dai, J., Wang, Q., Fan, Z., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47737-z · Cited by 92 · see citing works
“This suggested broad application of this platform in the rapid fabrication of cancer assembloid models even using microsamples such as biopsies that can be easily obtained from patients with intermediate and advanced tumor stages 38 .”
Advanced human developmental toxicity and teratogenicity assessment using human organoid models
Li, M., Gong, J., Gao, L., Zou, T., Kang, J., & Xu, H. (2022) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2022.113429 · Cited by 84 · see citing works
LGR5 marks targetable tumor-initiating cells in mouse liver cancer
Cao, W., Li, M., Liu, J., Zhang, S., Noordam, L., Verstegen, M. M. A., Wang, L., Ma, B., Li, S., Wang, W., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15846-0 · Cited by 82 · see citing works
Lim, J., Ching, H., Yoon, J., Jeon, N. L., & Kim, Y. (2021) · Nano Convergence · doi:10.1186/s40580-021-00261-y · Cited by 83 · see citing works
Organoid models for translational pancreatic cancer research
Tiriac, H., Plenker, D., Baker, L. A., & Tuveson, D. A. (2019) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2019.02.003 · Cited by 78 · see citing works
Transplant Oncology in Primary and Metastatic Liver Tumors
Sapisochín, G., Hibi, T., Toso, C., Man, K., Berenguer, M., Heimbach, J. K., Greten, T. F., Pugh, T. J., Dawson, L. A., & Mazzaferro, V. (2020) · Annals of Surgery · doi:10.1097/sla.0000000000004071 · Cited by 79 · see citing works
“Low resectability rate of hepato-biliary malignancies have long been the bottleneck of conducting genomic analyses using human tissue samples derived from needle biopsy.(78) Through collaborative repositories and data collections derived from transplant patients, abundant tumor tissue, and background liver parenchyma…”
BackgroundApplications of human organoids in the personalized treatment for digestive diseases
Wang, Q., Guo, F., Jin, Y., & Ma, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01194-6 · Cited by 81 · see citing works
“The generation of liver cancer (LC) organoids summarizes the molecular profiles of the corresponding tumor sources, including the PDO lineage of HCC, cholangiocarcinoma (CCC), and HCC/CCC combination; furthermore, lung metastases were found after transplantation into immunodeficient mice.(194,195) Biopsy-derived HCC/C…”
BackgroundExperimental Models of Hepatocellular Carcinoma—A Preclinical Perspective
Blidișel, A., Marcovici, I., Coricovac, D. E., Huţ, E. F., Dehelean, C. A., & Cretu, O. M. (2021) · Cancers · doi:10.3390/cancers13153651 · Cited by 78 · see citing works
“lated the features of the original biopsy in immunodeficient mice [102].”
BackgroundImmune organoids: from tumor modeling to precision oncology
Dao, V. A., Yuki, K., Lo, Y., Nakano, M., & Kuo, C. J. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.06.001 · Cited by 79 · see citing works
Choi, D., Gonzalez‐Suarez, A. M., Dumbrava, M. G., Medlyn, M. J., de Hoyos‐Vega, J. M., Cichocki, F. M., Miller, J. S., Li, D., Zhu, M., Stybayeva, G., et al. (2023) · Advanced Science · doi:10.1002/advs.202303088 · Cited by 73 · see citing works
Next-Generation Liver Medicine Using Organoid Models
Akbari, S., Arslan, N., Senturk, S., & Erdal, E. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00345 · Cited by 72 · see citing works
Drug screening model meets cancer organoid technology
Liu, C., Qin, T., Huang, Y., Li, Y., Chen, G., & Sun, C. (2020) · Translational Oncology · doi:10.1016/j.tranon.2020.100840 · Cited by 74 · see citing works
Organoids and Spheroids as Models for Studying Cholestatic Liver Injury and Cholangiocarcinoma
Sato, K., Zhang, W., Safarikia, S., Isidan, A., Chen, A. M., Li, P., Francis, H., Kennedy, L. L., Baiocchi, L., Alvaro, D., et al. (2020) · Hepatology · doi:10.1002/hep.31653 · Cited by 70 · see citing works
“(46) HCC and CCA organoids preserved histological characteristics and genetic alterations from original tumor tissues.(46) Patientderived organoids were treated with sorafenib and showed that the drug response could differ depending on individuals, suggesting the potential of organoids for designing personalized chemo…”
BackgroundInfluentialJung, M., Ghamrawi, S., Du, E. Y., Gooding, J. J., & Kavallaris, M. (2022) · Advanced Healthcare Materials · doi:10.1002/adhm.202200690 · Cited by 72 · see citing works
Novel patient-derived preclinical models of liver cancer.
Bresnahan, E. R., Ramadori, P., Heikenwalder, M., Zender, L., & Lujambio, A. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.09.028 · Cited by 63 · see citing works
Patient‐derived cancer organoids for drug screening: Basic technology and clinical application
Ren, X., Chen, W., Yang, Q., Li, X., & Xu, L. (2022) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.15930 · Cited by 69 · see citing works
Guo, K., Xiao, N.-Y., Liu, Y., Wang, Z.-M., Tóth, J., Gyenis, J., Thakur, V., Oyane, A., & Shubhra, Q. T. (2021) · Nano Materials Science · doi:10.1016/j.nanoms.2021.12.001 · Cited by 61 · see citing works
Atanasova, V. S., Cardona, C. D. J., Hejret, V., Tiefenbacher, A., Mair, T., Tran, L., Pfneissl, J., Draganić, K., Binder, C., Kabiljo, J., et al. (2023) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2023.02.014 · Cited by 67 · see citing works
“Organoid cancer models have shown great potential for precision medicine and there are living biobanks available, which are rapidly growing (37, 53, 54).”
BackgroundOrganotypic culture assays for murine and human primary and metastatic-site tumors
Padmanaban, V., Grasset, E. M., Neumann, N. M., Fraser, A. K., Henriet, E., Matsui, W. H., Tran, P. T., Cheung, K. J., Georgess, D., & Ewald, A. J. (2020) · Nature Protocols · doi:10.1038/s41596-020-0335-3 · Cited by 65 · see citing works
Xian, L., Zhao, P., Chen, X., Wei, Z., Ji, H., Zhao, J., Liu, W., Li, Z., Liu, D., Han, X., et al. (2022) · Cellular Oncology · doi:10.1007/s13402-022-00707-3 · Cited by 64 · see citing works
“Second, the success rate of establishing organoids is low, 26% in PLC [11].”
BackgroundResultTumor organoid biobank-new platform for medical research
Xie, X., Li, X., & Song, W. (2023) · Scientific Reports · doi:10.1038/s41598-023-29065-2 · Cited by 67 · see citing works
Human liver organoids: From generation to applications
Afonso, M. B., Marques, V., van Mil, S. W. C., & Rodrigues, C. M. P. (2024) · Hepatology · doi:10.1097/hep.0000000000000343 · Cited by 61 · see citing works
“Patient-derived organoids obtained from the tumor tissue of patients with liver cancer [29,30,88,115,117 – 120] are particularly useful as they resemble the histological architecture and genomic features of the original tumor in vitro and form tumors after subcutaneous xenotrans-plantation into…”
BackgroundInfluentialOrganoid models of the tumor microenvironment and their applications
Xia, T., Du, W., Chen, X., & Zhang, Y.-N. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16578 · Cited by 61 · see citing works
Chen, L., Wei, X., Gu, D., Xu, Y., & Zhou, H. (2023) · Cancer Letters · doi:10.1016/j.canlet.2022.216048 · Cited by 62 · see citing works
Breaking the mold: 3D cell cultures reshaping the future of cancer research
Cordeiro, S. Z., Oliveira, B. B. P. P., Valente, R., Ferreira, D., Luz, A., Baptista, P. V., & Fernandes, A. R. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1507388 · Cited by 64 · see citing works
“The process of obtaining primary tissues typically involves invasive procedures such as needle and endoscopic biopsies or surgical resections, which afterward are dissociated and cultured as previously explained (Gao et al., 2018; Nuciforo et al., 2018; Seidlitz et al., 2019).”
Dong, Y., Wong, J. S. L., Sugimura, R., Lam, K. O., Li, B. K., Kwok, G. W., Leung, R. C.-Y., Chiu, J. W. Y., Cheung, T. T., & Yau, T. C. C. (2021) · Cancers · doi:10.3390/cancers13081949 · Cited by 59 · see citing works
“Although HCC organoids can be established using a biopsy sample, immune cells are missing in these HCC organoids, presenting challenges for modeling ICI response [104].”
BackgroundPatient-Derived Organoids of Cholangiocarcinoma
Maier, C., Zhu, L., Nanduri, L. K., Kühn, D., Kochall, S., Thepkaysone, M.-L., William, D., Grützmann, K., Klink, B., Betge, J., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22168675 · Cited by 60 · see citing works
“Depending on the tumor entity, patient-derived organoids (PDOs) can be established from resected tumor tissues or core needle biopsies with higher success rates than classical CCLs, making PDOs an attractive in vitro model, especially for CC research [27,29,30].”
BackgroundThe role of organoids in cancer research
Fang, Z., Li, P., Du, F., Shang, L., & Li, L. (2023) · Experimental Hematology and Oncology · doi:10.1186/s40164-023-00433-y · Cited by 61 · see citing works
“In 2018, Nuciforo, S used patient biopsy tissue to construct liver cancer organoids for drug sensitivity testing [130].”
MethodResultTumor organoids: From inception to future in cancer research
Yang, L., Yang, S., Li, X., Li, B., Li, Y., Zhang, X., Ma, Y., Peng, X., Jin, H., Fan, Q., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.04.005 · Cited by 60 · see citing works
LATS1 but not LATS2 represses autophagy by a kinase-independent scaffold function
Tang, F., Gao, R., Jeevan-Raj, B. P., Wyss, C. B., Kalathur, R. K. R., Piscuoglio, S., Ng, C. K. Y., Hindupur, S. K., Nuciforo, S., Dazert, E., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13591-7 · Cited by 59 · see citing works
Self-citationShiota, J., Samuelson, L. C., & Razumilava, N. (2021) · Hepatology · doi:10.1002/hep.31772 · Cited by 57 · see citing works
“2253 homeostasis and rapid replacement after injury.(57)”
BackgroundInfluentialExploring liver cancer biology through functional genetic screens
Wang, C., Cao, Y., Yang, C. G., Bernards, R., & Qin, W. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00465-x · Cited by 58 · see citing works
Cox, C. R., Lynch, S., Goldring, C. E., & Sharma, P. (2020) · Frontiers in Medical Technology · doi:10.3389/fmedt.2020.611913 · Cited by 57 · see citing works
“Patient-derived tumor organoids are also capable of recapitulating the features of the original tumor in vitro, providing a model for identifying oncogenic mutations with prognostic value in liver cancer and identifying potential drug targets, enabling a personalized medicine approach and a patient-specific model for…”
BackgroundCancer organoids: A platform in basic and translational research
Ma, X., Wang, Q. L., Li, G., Li, H., Xu, S., & Pang, D. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.02.052 · Cited by 60 · see citing works
Ren, X., Huang, M., Weng, W., Xie, Y., Wu, Y., Zhu, S., Zhang, Y., Li, D., Lai, J., Shen, S., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101277 · Cited by 55 · see citing works
“18,19 Importantly, both the recurrent mutations (Figure S1C) and copy number alterations (Figure S1D) of the organoids recapitulated the genomic alterations in human BTC.”
BackgroundResultGranat, L. M., Kambhampati, O., Klosek, S., Niedzwecki, B., Parsa, K., & Zhang, D. (2019) · Animal Models and Experimental Medicine · doi:10.1002/ame2.12077 · Cited by 56 · see citing works
Progress in Animal Models of Pancreatic Ductal Adenocarcinoma
Kong, K., Guo, M., Liu, Y., & Zheng, J. (2020) · Journal of Cancer · doi:10.7150/jca.37529 · Cited by 54 · see citing works
“Indeed, several studies have reported that organoids can be derivedfrom needle biopsies taken from liver cancer [71], pancreatic cancer [72, 73], or humancolorectal cancer metastases [74].”
BackgroundProgress in human liver organoids
Sun, L., & Hui, L. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa013 · Cited by 55 · see citing works
Romualdo, G., Leroy, K., Costa, C. J. S., Prata, G., Vanderborght, B., Silva, T. C. D., Barbisan, L. F., Andraus, W., Devisscher, L., Câmara, N., et al. (2021) · Cancers · doi:10.3390/cancers13215583 · Cited by 45 · see citing works
Intratumoral heterogeneity of hepatocellular carcinoma: From single-cell to population-based studies
Zhang, Q., Lou, Y., Bai, X., & Liang, T. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i26.3720 · Cited by 52 · see citing works
Nguyen, R., Bae, S. D. W., Qiao, L., & George, J. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.03.017 · Cited by 50 · see citing works
Gastrointestinal cancer organoids—applications in basic and translational cancer research
Seidlitz, T., & Stange, D. E. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00654-3 · Cited by 49 · see citing works
Feng, J., Lu, H. J., Ma, W., Tian, W., Lu, Z., Yang, H., Cai, Y., Cai, P., Sun, Y., Zhou, Z., et al. (2022) · Protein & Cell · doi:10.1007/s13238-022-00906-6 · Cited by 49 · see citing works
“Organoids were generated according to previously described protocols (Broutier et al. 2017; Nuciforo et al. 2018) with slight modifications.”
Method
- Authors
- Nuciforo, S., Fofana, I., Matter, M. S., Blumer, T., Calabrese, D., Boldanova, T., Piscuoglio, S., Wieland, S., Ringnalda, F., Schwank, G., Terracciano, L. M., Ng, C. K. Y., & Heim, M. H.
- Affiliations
- University of Basel (CH)
- ETH Zurich (CH)
- Corresponding author
- Heim, Markus H.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 24
- Issue
- 5
- Pages
- 1363-1376
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6088153
- OpenAlex
- W2887409499
- Cited by
- 473
- References
- 49
- Citations by year
- 2026: 40 · 2025: 59 · 2024: 70 · 2023: 59 · 2022: 76 · 2021: 84 · 2020: 52 · 2019: 30 · 2018: 3
- FWCI
- 26.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- edoc (University of Basel) (acceptedVersion)
- Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by-nc-nd)
- ETH Zürich Research Collection
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (PZ00P3_168165)
- Marine Energy Research and Innovation Center (KFS-3995-08-2016)
- European Research Council (609883)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- hepatocellular carcinoma, sorafenib sensitivity, drug resistance, tumor heterogeneity, personalized treatment, in vitro tumor model, genetic heterogeneity
- MeSH terms
- Aged, Aged, 80 and over, Animals, Cells, Cultured, Female, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Organoids, Tissue Culture Techniques, Mice
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