{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T01:59:07Z","timestamp":1787795947994,"version":"build-2784847793"},"reference-count":132,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Organoids are a new 3D ex vivo culture system that have been applied in various fields of biomedical research. First isolated from the murine small intestine, they have since been established from a wide range of organs and tissues, both in healthy and diseased states. Organoids genetically, functionally and phenotypically retain the characteristics of their tissue of origin even after multiple passages, making them a valuable tool in studying various physiologic and pathophysiologic processes. The finding that organoids can also be established from tumor tissue or can be engineered to recapitulate tumor tissue has dramatically increased their use in cancer research. In this review, we discuss the potential of organoids to close the gap between preclinical in vitro and in vivo models as well as clinical trials in cancer research focusing on drug investigation and development.<\/jats:p>","DOI":"10.3390\/cancers13194812","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T01:59:47Z","timestamp":1632707987000},"page":"4812","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Organoid Models for Cancer Research\u2014From Bed to Bench Side and Back"],"prefix":"10.3390","volume":"13","author":[{"given":"Carolin","family":"Kastner","sequence":"first","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 6, 97080 Wuerzburg, Germany"},{"name":"Department of Biochemistry and Molecular Biology, University of Wuerzburg, Am Hubland, 97074 W\u00fcrzburg, Germany"},{"name":"Comprehensive Cancer Centre Mainfranken, University of Wuerzburg Medical Centre, Josef-Schneiderstr. 2, 97080 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Hendricks","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 6, 97080 Wuerzburg, Germany"},{"name":"Department of Biochemistry and Molecular Biology, University of Wuerzburg, Am Hubland, 97074 W\u00fcrzburg, Germany"},{"name":"Comprehensive Cancer Centre Mainfranken, University of Wuerzburg Medical Centre, Josef-Schneiderstr. 2, 97080 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Deinlein","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 6, 97080 Wuerzburg, Germany"},{"name":"Department of Biochemistry and Molecular Biology, University of Wuerzburg, Am Hubland, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Hankir","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 6, 97080 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph-Thomas","family":"Germer","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 6, 97080 Wuerzburg, Germany"},{"name":"Comprehensive Cancer Centre Mainfranken, University of Wuerzburg Medical Centre, Josef-Schneiderstr. 2, 97080 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2053-0909","authenticated-orcid":false,"given":"Stefanie","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 6, 97080 Wuerzburg, Germany"},{"name":"Department of Biochemistry and Molecular Biology, University of Wuerzburg, Am Hubland, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7777-0909","authenticated-orcid":false,"given":"Armin","family":"Wiegering","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital, University of Wuerzburg, Oberduerrbacherstr. 6, 97080 Wuerzburg, Germany"},{"name":"Department of Biochemistry and Molecular Biology, University of Wuerzburg, Am Hubland, 97074 W\u00fcrzburg, Germany"},{"name":"Comprehensive Cancer Centre Mainfranken, University of Wuerzburg Medical Centre, Josef-Schneiderstr. 2, 97080 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,26]]},"reference":[{"key":"ref_1","unstructured":"Ferlay, J., Ervik, M., Lam, F., Colombet, M., Mery, L., Pineros, M., Znaor, A., Soerjomataram, I., and Bray, F. (2018). Global Cancer Observatory: Cancer Today, International Agency for Research on Cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature11003","article-title":"The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity","volume":"483","author":"Barretina","year":"2012","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-019-1186-3","article-title":"Next-generation characterization of the Cancer Cell Line Encyclopedia","volume":"569","author":"Ghandi","year":"2019","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41568-018-0007-6","article-title":"Organoids in cancer research","volume":"18","author":"Drost","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/s41586-018-0409-3","article-title":"Genetic and transcriptional evolution alters cancer cell line drug response","volume":"560","author":"Siranosian","year":"2018","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1146\/annurev-pathmechdis-012419-032611","article-title":"Human Organoids: Tools for Understanding Biology and Treating Diseases","volume":"15","author":"Schutgens","year":"2020","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41580-020-0259-3","article-title":"Human organoids: Model systems for human biology and medicine","volume":"21","author":"Kim","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/biostatistics\/kxx069","article-title":"Estimation of clinical trial success rates and related parameters","volume":"20","author":"Wong","year":"2019","journal-title":"Biostatistics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/nbt.2786","article-title":"Clinical development success rates for investigational drugs","volume":"32","author":"Hay","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s12967-020-02677-2","article-title":"Patient-Derived Organoid (PDO) Platforms to Facilitate Clinical Decision Making","volume":"19","author":"Liu","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ejca.2017.05.034","article-title":"Universal Genomic Testing: The next step in oncological decision-making or a dead end street?","volume":"82","author":"Holch","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"dmm039347","DOI":"10.1242\/dmm.039347","article-title":"Disease modelling in human organoids","volume":"12","author":"Lancaster","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neo.2014.12.004","article-title":"Spherical Cancer Models in Tumor Biology","volume":"17","author":"Weiswald","year":"2015","journal-title":"Neoplasia"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Farhat, J., Pandey, I., and AlWahsh, M. (2021). Transcending toward Advanced 3D-Cell Culture Modalities: A Review about an Emerging Paradigm in Translational Oncology. Cells, 10.","DOI":"10.3390\/cells10071657"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.stem.2007.05.012","article-title":"Strategies and New Developments in the Generation of Patient-Specific Pluripotent Stem Cells","volume":"1","author":"Yamanaka","year":"2007","journal-title":"Cell Stem Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/nature09941","article-title":"Self-organizing optic-cup morphogenesis in three-dimensional culture","volume":"472","author":"Eiraku","year":"2011","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/nm.4233","article-title":"Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system","volume":"23","author":"Workman","year":"2017","journal-title":"Nat. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"8715","DOI":"10.1038\/ncomms9715","article-title":"Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids","volume":"6","author":"Freedman","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nature15695","article-title":"Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis","volume":"526","author":"Takasato","year":"2015","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/nature12517","article-title":"Cerebral organoids model human brain development and microcephaly","volume":"501","author":"Lancaster","year":"2013","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e94954","DOI":"10.1172\/jci.insight.94954","article-title":"Human hepatic organoids for the analysis of human genetic diseases","volume":"2","author":"Guan","year":"2017","journal-title":"JCI Insight"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.stemcr.2016.03.001","article-title":"Retinal Organoids from Pluripotent Stem Cells Efficiently Recapitulate Retinogenesis","volume":"6","author":"Rostovskaya","year":"2016","journal-title":"Stem Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1126\/science.1234852","article-title":"Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications","volume":"340","author":"Sato","year":"2013","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.cell.2016.05.082","article-title":"Modeling Development and Disease with Organoids","volume":"165","author":"Clevers","year":"2016","journal-title":"Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12861-020-0209-5","article-title":"Long-term expansion, genomic stability and in vivo safety of adult human pancreas organoids","volume":"20","author":"Georgakopoulos","year":"2020","journal-title":"BMC Dev. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.jcmgh.2019.11.013","article-title":"DNA Methylation Analysis Validates Organoids as a Viable Model for Studying Human Intestinal Aging","volume":"9","author":"Lewis","year":"2020","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1053\/j.gastro.2011.07.050","article-title":"Long-term Expansion of Epithelial Organoids From Human Colon, Adenoma, Adenocarcinoma, and Barrett\u2019s Epithelium","volume":"141","author":"Sato","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1016\/j.cell.2018.11.021","article-title":"Organoid Modeling of the Tumor Immune Microenvironment","volume":"175","author":"Neal","year":"2018","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Li, X., Ootani, A., and Kuo, C. (2016). An Air\u2013Liquid Interface Culture System for 3D Organoid Culture of Diverse Primary Gastroin-testinal Tissues. Gastrointestinal Physiology and Diseases, Humana Press.","DOI":"10.1007\/978-1-4939-3603-8_4"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1158\/2159-8290.CD-18-0689","article-title":"Suppression of STING Associated with LKB1 Loss in KRAS-Driven Lung Cancer","volume":"9","author":"Kitajima","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1158\/2159-8290.CD-17-0833","article-title":"Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids","volume":"8","author":"Jenkins","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1126\/science.aaw6985","article-title":"Cancer modeling meets human organoid technology","volume":"364","author":"Tuveson","year":"2019","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1056\/NEJM198809013190901","article-title":"Genetic Alterations during Colorectal-Tumor Development","volume":"319","author":"Vogelstein","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.humpath.2010.06.002","article-title":"Update on the serrated pathway to colorectal carcinoma","volume":"42","author":"Snover","year":"2011","journal-title":"Hum. Pathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1126\/science.aao3130","article-title":"Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer","volume":"358","author":"Drost","year":"2017","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/nm.3802","article-title":"Modeling colorectal cancer using CRISPR-Cas9\u2013mediated engineering of human intestinal organoids","volume":"21","author":"Matano","year":"2015","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E2357","DOI":"10.1073\/pnas.1701219114","article-title":"Genetic dissection of colorectal cancer progression by orthotopic transplantation of engineered cancer organoids","volume":"114","author":"Fumagalli","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1083\/jcb.201506014","article-title":"GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells","volume":"211","author":"Gao","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1136\/gutjnl-2017-315920","article-title":"Genetic editing of colonic organoids provides a molecularly distinct and orthotopic preclinical model of serrated carcinogenesis","volume":"68","author":"Lannagan","year":"2019","journal-title":"Gut"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.canlet.2018.08.017","article-title":"Modeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids","volume":"436","author":"Liu","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"745","DOI":"10.15252\/emmm.201606184","article-title":"TGF\u03b2 signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype","volume":"8","author":"Fessler","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-014-0428-9","article-title":"Metastatic tumor evolution and organoid modeling implicate TGFBR2as a cancer driver in diffuse gastric cancer","volume":"15","author":"Nadauld","year":"2014","journal-title":"Genome Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/nature14415","article-title":"Sequential cancer mutations in cultured human intestinal stem cells","volume":"521","author":"Drost","year":"2015","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1093\/jnci\/djz196","article-title":"Modeling Breast Cancer Using CRISPR-Cas9\u2013Mediated Engineering of Human Breast Organoids","volume":"112","author":"Dekkers","year":"2020","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1053\/j.gastro.2019.10.009","article-title":"Chromosome Engineering of Human Colon-Derived Organoids to Develop a Model of Traditional Serrated Adenoma","volume":"158","author":"Kawasaki","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.stem.2017.12.009","article-title":"Human Pancreatic Tumor Organoids Reveal Loss of Stem Cell Niche Factor Dependence during Disease Progression","volume":"22","author":"Seino","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00109-020-02029-z","article-title":"Genetic Engineering in Organoids","volume":"99","author":"Teriyapirom","year":"2021","journal-title":"J. Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/j.celrep.2018.03.105","article-title":"Glioblastoma Model Using Human Cerebral Organoids","volume":"23","author":"Ogawa","year":"2018","journal-title":"Cell Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1101\/gad.339978.120","article-title":"SMARCB1 loss interacts with neuronal differentiation state to block maturation and impact cell stability","volume":"34","author":"Parisian","year":"2020","journal-title":"Genes Dev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ebiom.2019.03.064","article-title":"Gene signatures of quiescent glioblastoma cells reveal mesenchymal shift and interactions with niche microenvironment","volume":"42","author":"Huang","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"13308","DOI":"10.1073\/pnas.1516689112","article-title":"Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases","volume":"112","author":"Weeber","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.stem.2016.04.003","article-title":"A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis","volume":"18","author":"Fujii","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1038\/s41591-019-0584-2","article-title":"A rectal cancer organoid platform to study individual responses to chemoradiation","volume":"25","author":"Ganesh","year":"2019","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"5376","DOI":"10.1158\/1078-0432.CCR-18-3590","article-title":"Patient-Derived Cancer Organoid Cultures to Predict Sensitivity to Chemotherapy and Radiation","volume":"25","author":"Pasch","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1038\/nm.4438","article-title":"Human primary liver cancer\u2013derived organoid cultures for disease modeling and drug screening","volume":"23","author":"Broutier","year":"2017","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Maier, C.F., Zhu, L., Nanduri, L.K., K\u00fchn, D., Kochall, S., Thepkaysone, M.-L., William, D., Gr\u00fctzmann, K., Klink, B., and Betge, J. (2021). Patient-Derived Organoids of Cholangiocarcinoma. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168675"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.scr.2018.01.016","article-title":"Colorectal cancer liver metastases organoids retain characteristics of original tumor and acquire chemotherapy resistance","volume":"27","author":"Buzzelli","year":"2018","journal-title":"Stem Cell Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.cell.2014.08.016","article-title":"Organoid Cultures Derived from Patients with Advanced Prostate Cancer","volume":"159","author":"Gao","year":"2014","journal-title":"Cell"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12383","DOI":"10.18632\/oncotarget.2592","article-title":"Expansion of CTCs from early stage lung cancer patients using a microfluidic co-culture model","volume":"5","author":"Zhang","year":"2014","journal-title":"Oncotarget"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.cell.2017.11.010","article-title":"A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity","volume":"172","author":"Sachs","year":"2018","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.cell.2015.03.053","article-title":"Prospective Derivation of a Living Organoid Biobank of Colorectal Cancer Patients","volume":"161","author":"Francies","year":"2015","journal-title":"Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1093\/gastro\/goy040","article-title":"Patient-derived organoids: A promising model for personalized cancer treatment","volume":"6","author":"Yang","year":"2018","journal-title":"Gastroenterol. Rep."},{"key":"ref_66","first-page":"1","article-title":"Patient-derived organoids as a predictive biomarker for treatment response in cancer patients","volume":"5","author":"Wensink","year":"2021","journal-title":"NPJ Precis. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1016\/j.gie.2017.12.032","article-title":"Successful creation of pancreatic cancer organoids by means of EUS-guided fine-needle biopsy sampling for personalized cancer treatment","volume":"87","author":"Tiriac","year":"2018","journal-title":"Gastrointest. Endosc."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jcmgh.2018.09.003","article-title":"Three-Dimensional Organoids Reveal Therapy Resistance of Esophageal and Oropharyngeal Squamous Cell Carcinoma Cells","volume":"7","author":"Kijima","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_69","first-page":"1","article-title":"Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics","volume":"9","author":"Li","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.stem.2018.09.016","article-title":"A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening","volume":"23","author":"Yan","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1073\/pnas.1803595116","article-title":"Mouse and human urothelial cancer organoids: A tool for bladder cancer research","volume":"116","author":"Mullenders","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.celrep.2018.07.001","article-title":"Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies","volume":"24","author":"Nuciforo","year":"2018","journal-title":"Cell Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.celrep.2019.03.088","article-title":"Establishment of Patient-Derived Organoids and Drug Screening for Biliary Tract Carcinoma","volume":"27","author":"Saito","year":"2019","journal-title":"Cell Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"26580","DOI":"10.1073\/pnas.1911273116","article-title":"Pancreatic cancer organoids recapitulate disease and allow personalized drug screening","volume":"116","author":"Driehuis","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1158\/2159-8290.CD-18-0349","article-title":"Organoid Profiling Identifies Common Responders to Chemotherapy in Pancreatic Cancer","volume":"8","author":"Tiriac","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/path.5515","article-title":"Molecular characterization of organoids derived from pancreatic intraductal papillary mucinous neoplasms","volume":"252","author":"Huang","year":"2020","journal-title":"J. Pathol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/s41374-020-00494-1","article-title":"Establishing a living biobank of patient-derived organoids of intraductal papillary mucinous neoplasms of the pancreas","volume":"101","author":"Beato","year":"2021","journal-title":"Lab. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1016\/j.cell.2020.10.023","article-title":"An Organoid Biobank of Neuroendocrine Neoplasms Enables Genotype-Phenotype Mapping","volume":"183","author":"Kawasaki","year":"2020","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"430","DOI":"10.4149\/neo_2020_190417N346","article-title":"Patient-derived organoids of non-small cells lung cancer and their application for drug screening","volume":"67","author":"Li","year":"2020","journal-title":"Neoplasma"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-11867-6","article-title":"Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening","volume":"10","author":"Kim","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"101411","DOI":"10.1016\/j.isci.2020.101411","article-title":"Human Lung Adenocarcinoma-Derived Organoid Models for Drug Screening","volume":"23","author":"Li","year":"2020","journal-title":"iScience"},{"key":"ref_82","first-page":"1","article-title":"Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week","volume":"12","author":"Hu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.cell.2019.11.036","article-title":"A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity","volume":"180","author":"Jacob","year":"2019","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.cell.2018.03.017","article-title":"Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer","volume":"173","author":"Lee","year":"2018","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-020-15155-6","article-title":"An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity","volume":"11","author":"Calandrini","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12575-019-0099-8","article-title":"Establishment and Morphological Characterization of Patient-Derived Organoids from Breast Cancer","volume":"21","author":"Mazzucchelli","year":"2019","journal-title":"Biol. Proced. Online"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1158\/1541-7786.MCR-19-0453","article-title":"Genomic Characteristics of Triple-Negative Breast Cancer Nominate Molecular Subtypes That Predict Chemotherapy Response","volume":"18","author":"Kim","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Campaner, E., Zannini, A., Santorsola, M., Bonazza, D., Bottin, C., Cancila, V., Tripodo, C., Bortul, M., Zanconati, F., and Schoeftner, S. (2020). Breast Cancer Organoids Model Patient-Specific Response to Drug Treatment. Cancers, 12.","DOI":"10.3390\/cancers12123869"},{"key":"ref_89","first-page":"17","article-title":"Organoid Biobanks as a New Tool for Pre-Clinical Validation of Candidate Drug Effi-cacy and Safety","volume":"13","author":"Botti","year":"2021","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1126\/science.aao2774","article-title":"Patient-derived organoids model treatment response of metastatic gastrointestinal cancers","volume":"359","author":"Vlachogiannis","year":"2018","journal-title":"Science"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"eaay2574","DOI":"10.1126\/scitranslmed.aay2574","article-title":"Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients","volume":"11","author":"Ooft","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"S106","DOI":"10.1016\/j.ijrobp.2019.06.597","article-title":"Patient-Derived Organoids (PDO) As the Potential Model to Predict Treatment Outcome of Rectal Cancer Patients Underwent Neo-Adjuvant Chemoradiotherapy","volume":"105","author":"Yao","year":"2019","journal-title":"Int. J. Radiat. Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.gde.2019.02.003","article-title":"Organoid models for translational pancreatic cancer research","volume":"54","author":"Tiriac","year":"2019","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1158\/1541-7786.MCR-18-0531","article-title":"Human Organoids Share Structural and Genetic Features with Primary Pancreatic Adenocarcinoma Tumors","volume":"17","author":"Weber","year":"2019","journal-title":"Mol. Cancer Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1158\/2159-8290.CD-18-1522","article-title":"Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy","volume":"9","author":"Driehuis","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Beutel, A., Sch\u00fctte, L., Scheible, J., Roger, E., M\u00fcller, M., Perkhofer, L., Kestler, A., Kraus, J., Kestler, H., and Barth, T. (2021). A Prospective Feasibility Trial to Challenge Patient\u2013Derived Pancreatic Cancer Organoids in Predicting Treatment Response. Cancers, 13.","DOI":"10.3390\/cancers13112539"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1158\/1078-0432.CCR-20-0073","article-title":"Medium-throughput Drug Screening of Patient-derived Organoids from Colorectal Peritoneal Metastases to Direct Personalized Therapy","volume":"26","author":"Narasimhan","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"100103","DOI":"10.1016\/j.esmoop.2021.100103","article-title":"Prospective experimental treatment of colorectal cancer patients based on organoid drug responses","volume":"6","author":"Ooft","year":"2021","journal-title":"ESMO Open"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"820","DOI":"10.3389\/fonc.2021.641980","article-title":"Patient-Derived Cancer Organoids as Predictors of Treatment Response","volume":"11","author":"Verduin","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-71589-4","article-title":"Towards personalized induction therapy for esophageal adenocarcinoma: Organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor","volume":"10","author":"Derouet","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jcmgh.2018.09.008","article-title":"An Organoid-Based Preclinical Model of Human Gastric Cancer","volume":"7","author":"Steele","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1007\/s00432-019-03004-z","article-title":"Malignant ascites-derived organoid (MADO) cultures for gastric cancer in vitro modelling and drug screening","volume":"145","author":"Li","year":"2019","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.stem.2019.10.010","article-title":"Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer","volume":"26","author":"Yao","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1177\/2050640620905183","article-title":"Pancreatic cancer-derived organoids\u2014A disease modeling tool to predict drug response","volume":"8","author":"Frappart","year":"2020","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Guillen, K., Fujita, M., Butterfield, A., and Scherer, S. (2021). A Breast Cancer Patient-Derived Xenograft and Organoid Platform for Drug Discovery and Precision Oncology. bioRxiv.","DOI":"10.1101\/2021.02.28.433268"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"107762","DOI":"10.1016\/j.celrep.2020.107762","article-title":"Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses","volume":"31","author":"Hami","year":"2020","journal-title":"Cell Rep."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1245\/s10434-019-08143-8","article-title":"Model of Patient-Specific Immune-Enhanced Organoids for Immunotherapy Screening: Feasibility Study","volume":"27","author":"Votanopoulos","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1038\/s41591-019-0422-6","article-title":"An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity","volume":"25","author":"Kopper","year":"2019","journal-title":"Nat. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-019-0832-4","article-title":"Emerging organoid models: Leaping forward in cancer research","volume":"12","author":"Fan","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_110","unstructured":"ClinicalTrials.gov (2021, April 01). U.S. National Library of Medicine, Available online: https:\/\/Clinicaltrials.Gov."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e18489","DOI":"10.7554\/eLife.18489","article-title":"Targeting mutant RAS in patient-derived colorectal cancer organoids by combinatorial drug screening","volume":"5","author":"Verissimo","year":"2016","journal-title":"eLife"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"6742","DOI":"10.1158\/1078-0432.CCR-19-1398","article-title":"Identification of Resistance Pathways Specific to Malignancy Using Organoid Models of Pancreatic Cancer","volume":"25","author":"Corbo","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1158\/2159-8290.CD-16-1154","article-title":"Personalized In Vitro and In Vivo Cancer Models to Guide Precision Medicine","volume":"7","author":"Pauli","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"949","DOI":"10.3389\/fphar.2017.00949","article-title":"Rimonabant Kills Colon Cancer Stem Cells without Inducing Toxicity in Normal Colon Organoids","volume":"8","author":"Fiore","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1124\/dmd.117.075945","article-title":"Crypt Organoid Culture as an in Vitro Model in Drug Metabolism and Cytotoxicity Studies","volume":"45","author":"Lu","year":"2017","journal-title":"Drug Metab. Dispos."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.taap.2018.02.003","article-title":"Rotenone exerts developmental neurotoxicity in a human brain spheroid model","volume":"354","author":"Pamies","year":"2018","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.drudis.2019.11.010","article-title":"CNS organoids: An innovative tool for neurological disease modeling and drug neurotoxicity screening","volume":"25","author":"Chhibber","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"417","DOI":"10.3389\/fphy.2020.568027","article-title":"Solving the Issue of Ionizing Radiation Induced Neurotoxicity by Using Novel Cell Models and State of the Art Accelerator Facilities","volume":"8","author":"Schielke","year":"2020","journal-title":"Front. Phys."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.neuroscience.2018.12.047","article-title":"Vincristine Impairs Microtubules and Causes Neurotoxicity in Cerebral Organoids","volume":"404","author":"Liu","year":"2019","journal-title":"Neuroscience"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2015.11.026","article-title":"Novel human hepatic organoid model enables testing of drug-induced liver fibrosis in vitro","volume":"78","author":"Leite","year":"2016","journal-title":"Biomaterials"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/j.jhep.2019.06.030","article-title":"Generation of expandable human pluripotent stem cell-derived hepatocyte-like liver organoids","volume":"71","author":"Mun","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Driehuis, E., Oosterom, N., Heil, S.G., Muller, I.B., Lin, M., Kolders, S., Jansen, G., De Jonge, R., Pieters, R., and Clevers, H. (2020). Patient-derived oral mucosa organoids as an in vitro model for methotrexate induced toxicity in pediatric acute lymphoblastic leukemia. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0237488"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-cancerbio-030518-055702","article-title":"Organoid Models for Cancer Research","volume":"3","author":"Clevers","year":"2019","journal-title":"Annu. Rev. Cancer Biol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.it.2020.06.010","article-title":"Organoid Models of Tumor Immunology","volume":"41","author":"Yuki","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41596-019-0232-9","article-title":"Tumor organoid\u2013T-cell coculture systems","volume":"15","author":"Cattaneo","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.cell.2018.07.009","article-title":"Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids","volume":"174","author":"Dijkstra","year":"2018","journal-title":"Cell"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Tsai, S., McOlash, L., Palen, K., Johnson, B., Duris, C., Yang, Q., Dwinell, M.B., Hunt, B., Evans, D.B., and Gershan, J. (2018). Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4238-4"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"37439","DOI":"10.18632\/oncotarget.26473","article-title":"Hedgehog signaling induces PD-L1 expression and tumor cell proliferation in gastric cancer","volume":"9","author":"Chakrabarti","year":"2018","journal-title":"Oncotarget"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"66747","DOI":"10.18632\/oncotarget.19965","article-title":"Application of 3D tumoroid systems to define immune and cytotoxic therapeutic responses based on tumoroid and tissue slice culture molecular signatures","volume":"8","author":"Finnberg","year":"2017","journal-title":"Oncotarget"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fbioe.2019.00039","article-title":"Engineering Organoid Vascularization","volume":"7","author":"Grebenyuk","year":"2019","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1039\/D0LC01186J","article-title":"Vascularized organoids on a chip: Strategies for engineering organoids with functional vasculature","volume":"21","author":"Zhang","year":"2021","journal-title":"Lab Chip"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41578-021-00279-y","article-title":"Engineering organoids","volume":"6","author":"Hofer","year":"2021","journal-title":"Nat. Rev. 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