Abstract
Organotypic models of patient-specific tumours are revolutionizing our understanding of cancer heterogeneity and its implications for personalized medicine. These advancements are, in part, attributed to the ability of organoid models to stably preserve genetic, proteomic, morphological and pharmacotypic features of the parent tumour in vitro, while also offering unprecedented genomic and environmental manipulation. Despite recent innovations in organoid protocols, current techniques for cancer organoid culture are inherently uncontrolled and irreproducible, owing to several non-standardized facets including cancer tissue sources and subsequent processing, medium formulations, and animal-derived three-dimensional matrices. Given the potential for cancer organoids to accurately recapitulate the intra- and intertumoral biological heterogeneity associated with patient-specific cancers, eliminating the undesirable technical variability accompanying cancer organoid culture is necessary to establish reproducible platforms that accelerate translatable insights into patient care. Here we describe the current challenges and recent multidisciplinary advancements and opportunities for standardizing next-generation cancer organoid systems.
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References
Bedard, P. L., Hansen, A. R., Ratain, M. J. & Siu, L. L. Tumour heterogeneity in the clinic. Nature 501, 355–364 (2013).
Dagogo-Jack, I. & Shaw, A. T. Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 15, 81–94 (2018).
Catenacci, D. V. T. Next-generation clinical trials: novel strategies to address the challenge of tumor molecular heterogeneity. Mol. Oncol. 9, 967–996 (2015).
Turajlic, S., Sottoriva, A., Graham, T. & Swanton, C. Resolving genetic heterogeneity in cancer. Nat. Rev. Genet. 20, 404–416 (2019).
Meacham, C. E. & Morrison, S. J. Tumour heterogeneity and cancer cell plasticity. Nature 501, 328–337 (2013).
Marusyk, A., Janiszewska, M. & Polyak, K. Intratumor heterogeneity: the Rosetta Stone of therapy resistance. Cancer Cell 37, 471–484 (2020).
Runa, F. et al. Tumor microenvironment heterogeneity: challenges and opportunities. Curr. Mol. Biol. Rep. 3, 218–229 (2017).
Qian, J. et al. A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling. Cell Res. 30, 745–762 (2020).
Drost, J. & Clevers, H. Organoids in cancer research. Nat. Rev. Cancer 18, 407–418 (2018).
Sato, T. et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141, 1762–1772 (2011).
Sato, T. et al. Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche. Nature 459, 262–265 (2009).
Vlachogiannis, G. et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science 359, 920–926 (2018).
Tiriac, H. et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov. 8, 1112–1129 (2018).
Kopper, O. et al. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity. Nat. Med. 25, 838–849 (2019).
Sachs, N. et al. A living biobank of breast cancer organoids captures disease heterogeneity. Cell 172, 373–386.e10 (2018).
Neal, J. T. et al. Organoid modeling of the tumor immune microenvironment. Cell 175, 1972–1988.e16 (2018).
Ganesh, K. et al. A rectal cancer organoid platform to study individual responses to chemoradiation. Nat. Med. 25, 1607–1614 (2019).
Fujii, M. et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 18, 827–838 (2016).
Nanki, K. et al. Divergent routes toward Wnt and R-spondin niche independency during human gastric carcinogenesis. Cell 174, 856–869.e17 (2018).
Seino, T. et al. Human pancreatic tumor organoids reveal loss of stem cell niche factor dependence during disease progression. Cell Stem Cell 22, 454–467.e6 (2018).
Boj, S. F. et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 160, 324–338 (2015).
Kodack, D. P. et al. Primary patient-derived cancer cells and their potential for personalized cancer patient care. Cell Rep. 21, 3298–3309 (2017).
Öhlund, D. et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J. Exp. Med. 214, 579–596 (2017).
van de Wetering, M. et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161, 933–945 (2015).
Gao, D. et al. Organoid cultures derived from patients with advanced prostate cancer. Cell 159, 176–187 (2014).
Hill, S. J. et al. Prediction of DNA repair inhibitor response in short-term patient-derived ovarian cancer organoids. Cancer Discov. 8, 1404–1421 (2018).
Lee, S. H. et al. Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173, 515–528.e17 (2018).
Broutier, L. et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat. Med. 23, 1424–1435 (2017).
Kim, M. et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat. Commun. 10, 3991 (2019).
Sachs, N. et al. Long‐term expanding human airway organoids for disease modeling. EMBO J. 38, 1–20 (2019).
Li, X. et al. Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics. Nat. Commun. 9, 2983 (2018).
Boretto, M. et al. Patient-derived organoids from endometrial disease capture clinical heterogeneity and are amenable to drug screening. Nat. Cell Biol. 21, 1041–1051 (2019).
Jacob, F. et al. A patient-derived glioblastoma organoid model and biobank recapitulates inter- and intra-tumoral heterogeneity. Cell 180, 188–204.e22 (2020).
Dijkstra, K. K. et al. Challenges in establishing pure lung cancer organoids limit their utility for personalized medicine. Cell Rep. 31, 107588 (2020).
Calandrini, C. et al. An organoid biobank for childhood kidney cancers that captures disease and tissue heterogeneity. Nat. Commun. 11, 1310 (2020).
Bock, C. et al. The Organoid Cell Atlas. Nat. Biotechnol. 39, 13–17 (2021).
Baker, L. A., Tiriac, H., Clevers, H. & Tuveson, D. A. Modeling pancreatic cancer with organoids. Trends Cancer 2, 176–190 (2016).
Driehuis, E., Kretzschmar, K. & Clevers, H. Establishment of patient-derived cancer organoids for drug-screening applications. Nat. Protoc. 15, 3380–3409 (2020).
Roerink, S. F. et al. Intra-tumour diversification in colorectal cancer at the single-cell level. Nature 556, 437–462 (2018).
Walsh, A. J., Cook, R. S., Sanders, M. E., Arteaga, C. L. & Skala, M. C. Drug response in organoids generated from frozen primary tumor tissues. Sci. Rep. 6, 18889 (2016).
Brandenberg, N. et al. High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays. Nat. Biomed. Eng. 4, 863–874 (2020).
Horowitz, L. F. et al. Microdissected ‘cuboids’ for microfluidic drug testing of intact tissues. Lab Chip 21, 122–142 (2021).
Li, X. et al. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat. Med. 20, 769–777 (2014).
Dimarco, R. L. et al. Engineering of three-dimensional microenvironments to promote contractile behavior in primary intestinal organoids. Integr. Biol. 6, 127–142 (2014).
Schnalzger, T. E. et al. 3D model for CAR-mediated cytotoxicity using patient-derived colorectal cancer organoids. EMBO J. 38, e100928 (2019).
Ebbing, E. A. et al. Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma. Proc. Natl Acad. Sci. USA 116, 2237–2242 (2019).
Umkehrer, C. et al. Isolating live cell clones from barcoded populations using CRISPRa-inducible reporters. Nat. Biotechnol. 39, 174–178 (2021).
Kassis, T., Hernandez-Gordillo, V., Langer, R. & Griffith, L. G. OrgaQuant: human intestinal organoid localization and quantification using deep convolutional neural networks. Sci. Rep. 9, 12479 (2019).
Haase, K., Offeddu, G. S., Gillrie, M. R. & Kamm, R. D. Endothelial regulation of drug transport in a 3D vascularized tumor model. Adv. Funct. Mater. 30, 2002444 (2020).
Chen, M. B. et al. On-chip human microvasculature assay for visualization and quantification of tumor cell extravasation dynamics. Nat. Protoc. 12, 865–880 (2017).
Nikolaev, M. et al. Homeostatic mini-intestines through scaffold-guided organoid morphogenesis. Nature 585, 574–578 (2020).
Willert, K. et al. Wnt proteins are lipid-modified and can act as stem cell growth factors. Nature 423, 448–452 (2003).
Tüysüz, N. et al. Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells. Nat. Commun. 8, 2014–1723 (2017).
Johnson, M. Fetal bovine serum. Mater. Methods 2, 117 (2012).
Anderson, N. L. et al. The human plasma proteome. Mol. Cell. Proteom. 3, 311–326 (2004).
van der Valk, J. et al. Optimization of chemically defined cell culture media—replacing fetal bovine serum in mammalian in vitro methods. Toxicol. Vitr. 24, 1053–1063 (2010).
Mihara, E. et al. Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin. eLife 5, e11621 (2016).
Urbischek, M. et al. Organoid culture media formulated with growth factors of defined cellular activity. Sci. Rep. 9, 6193 (2019).
Janda, C. Y. et al. Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling. Nature 545, 234–237 (2017).
Miao, Y. et al. Next-generation surrogate Wnts support organoid growth and deconvolute Frizzled pleiotropy in vivo. Cell Stem Cell 27, 840-851.E6 (2020).
Luca, V. C. et al. Surrogate R-spondins for tissue-specific potentiation of Wnt signaling. PLoS ONE 15, e0226928 (2020).
Tsukamoto, A. S., Grosschedl, R., Guzman, R. C., Parslow, T. & Varmus, H. E. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell 55, 619–625 (1988).
Kumar, M. P. et al. Analysis of single-cell RNA-seq identifies cell–cell communication associated with tumor characteristics. Cell Rep. 25, 1458–1468.e4 (2018).
Broguiere, N. et al. Morphogenesis guided by 3D patterning of growth factors in biological matrices. Adv. Mater. 32, 1908299 (2020).
Henke, E., Nandigama, R. & Ergün, S. Extracellular matrix in the tumor microenvironment and its impact on cancer therapy. Front. Mol. Biosci. 6, 160 (2020).
Nia, H. T., Munn, L. L. & Jain, R. K. Physical traits of cancer. Science 370, eaaz0868 (2020).
Sheridan, C. Pancreatic cancer provides testbed for first mechanotherapeutics. Nat. Biotechnol. 37, 829–831 (2019).
Weaver, V. M. et al. Β4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2, 205–216 (2002).
Kenny, P. A. et al. The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Mol. Oncol. 1, 84–96 (2007).
Corning Matrigel Matrix: Frequently Asked Questions (Corning, 2019); https://www.corning.com/catalog/cls/documents/faqs/CLS-DL-CC-026.pdf
Aisenbrey, E. A. & Murphy, W. L. Synthetic alternatives to Matrigel. Nat. Rev. Mater. 5, 539–551 (2020).
Hughes, C. S., Postovit, L. M. & Lajoie, G. A. Matrigel: a complex protein mixture required for optimal growth of cell culture. Proteomics 10, 1886–1890 (2010).
Acerbi, I. et al. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr. Biol. 7, 1120–1134 (2015).
Slater, K., Partridge, J. & Nandivada, H. Tuning the Elastic Moduli of Corning Matrigel and Collagen I 3D Matrices by Varying the Protein Concentration (Corning, 2019); https://www.corning.com/catalog/cls/documents/application-notes/CLS-AC-AN-449.pdf
Lu, P., Weaver, V. M. & Werb, Z. The extracellular matrix: a dynamic niche in cancer progression. J. Cell Biol. 196, 395–406 (2012).
Hapach, L. A., Vanderburgh, J. A., Miller, J. P. & Reinhart-King, C. A. Manipulation of in vitro collagen matrix architecture for scaffolds of improved physiological relevance. Phys. Biol. 12, 061002 (2015).
Velez, D. O. et al. 3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry. Nat. Commun. 8, 1651 (2017).
Liu, Z. & Vunjak-Novakovic, G. Modeling tumor microenvironments using custom-designed biomaterial scaffolds. Curr. Opin. Chem. Eng. 11, 94–105 (2016).
Gu, L. & Mooney, D. J. Biomaterials and emerging anticancer therapeutics: engineering the microenvironment. Nat. Rev. Cancer 16, 56–66 (2016).
Xiao, W. et al. Brain-mimetic 3D culture platforms allow investigation of cooperative effects of extracellular matrix features on therapeutic resistance in glioblastoma. Cancer Res. 78, 1358–1370 (2018).
Kratochvil, M. J. et al. Engineered materials for organoid systems. Nat. Rev. Mater. 4, 606–622 (2019).
Gjorevski, N. et al. Designer matrices for intestinal stem cell and organoid culture. Nature 539, 560–564 (2016).
Rezakhani, S., Gjorevski, N. & Lutolf, M. P. Low-defect thiol–Michael addition hydrogels as Matrigel substitutes for epithelial organoid derivation. Adv. Funct. Mater. 30, 2000761 (2020).
Cruz-Acuña, R. et al. Synthetic hydrogels for human intestinal organoid generation and colonic wound repair. Nat. Cell Biol. 19, 1326–1335 (2017).
Hernandez-Gordillo, V. et al. Fully synthetic matrices for in vitro culture of primary human intestinal enteroids and endometrial organoids. Biomaterials 254, 120125 (2020).
Chen, Y., Zhou, W., Roh, T., Estes, M. K. & Kaplan, D. L. In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses. PLoS ONE 12, e0187880 (2017).
Capeling, M. M. et al. Nonadhesive alginate hydrogels support growth of pluripotent stem cell-derived intestinal organoids. Stem Cell Rep. 12, 381–394 (2019).
Broguiere, N. et al. Growth of epithelial organoids in a defined hydrogel. Adv. Mater. 30, e1801621 (2018).
DiMarco, R. L., Dewi, R. E., Bernal, G., Kuo, C. & Heilshorn, S. C. Protein-engineered scaffolds for in vitro 3D culture of primary adult intestinal organoids. Biomater. Sci. 3, 1376–1385 (2015).
Hunt, D. R. et al. Engineered matrices enable the culture of human patient-derived intestinal organoids. Adv. Sci. 8, 2004705 (2021).
DeForest, C. A. & Tirrell, D. A. A photoreversible protein-patterning approach for guiding stem cell fate in three-dimensional gels. Nat. Mater. 14, 523–531 (2015).
Stowers, R. S., Allen, S. C. & Suggs, L. J. Dynamic phototuning of 3D hydrogel stiffness. Proc. Natl Acad. Sci. USA 112, 1953–1958 (2015).
Hushka, E. A., Yavitt, F. M., Brown, T. E., Dempsey, P. J. & Anseth, K. S. Relaxation of extracellular matrix forces directs crypt formation and architecture in intestinal organoids. Adv. Healthc. Mater. 9, 1901214 (2020).
Brassard, J. A., Nikolaev, M., Hübscher, T., Hofer, M. & Lutolf, M. P. Recapitulating macro-scale tissue self-organization through organoid bioprinting. Nat. Mater. 20, 22–29 (2021).
Krajina, B. A. et al. Microrheology reveals simultaneous cell-mediated matrix stiffening and fluidization that underlie breast cancer invasion. Sci. Adv. 7, eabe1969 (2021).
Crespo, M. et al. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing. Nat. Med. 23, 878–884 (2017).
Forbes, T. A. et al. Patient-iPSC-derived kidney organoids show functional validation of a ciliopathic renal phenotype and reveal underlying pathogenetic mechanisms. Am. J. Hum. Genet. 102, 816–831 (2018).
Cruz, N. M. et al. Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease. Nat. Mater. 16, 1112–1119 (2017).
Linnemann, J. R. et al. Quantification of regenerative potential in primary human mammary epithelial cells. Development 142, 3239–3251 (2015).
Rocco, S. A. et al. Cadmium exposure inhibits branching morphogenesis and causes alterations consistent with HIF-1α inhibition in human primary breast organoids. Toxicol. Sci. 164, 592–602 (2018).
Cha, J., Kang, S. G. & Kim, P. Strategies of mesenchymal invasion of patient-derived brain tumors: microenvironmental adaptation. Sci. Rep. 6, 24912 (2016).
Wilkinson, D. C. et al. Development of a three-dimensional bioengineering technology to generate lung tissue for personalized disease modeling. Stem Cells Transl. Med. 6, 622–633 (2017).
Ng, S. S. et al. Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly(ethylene glycol) scaffold. Biomaterials 182, 299–311 (2018).
Rajasekar, S. et al. IFlowPlate—a customized 384-well plate for the culture of perfusable vascularized colon organoids. Adv. Mater. 32, 2002974 (2020).
Lindborg, B. A. et al. Rapid induction of cerebral organoids from human induced pluripotent stem cells using a chemically defined hydrogel and defined cell culture medium. Stem Cells Transl. Med. 5, 970–979 (2016).
Astashkina, A. I. et al. Nanoparticle toxicity assessment using an in vitro 3-D kidney organoid culture model. Biomaterials 35, 6323–6331 (2014).
Bejoy, J. et al. Differential effects of heparin and hyaluronic acid on neural patterning of human induced pluripotent stem cells. ACS Biomater. Sci. Eng. 4, 4354–4366 (2018).
Kaemmerer, E. et al. Gelatine methacrylamide-based hydrogels: an alternative three-dimensional cancer cell culture system. Acta Biomater. 10, 2551–2562 (2014).
Zhang, Y. S. et al. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc. Natl Acad. Sci. USA 114, E2293–E2302 (2017).
Töpfer, E. et al. Bovine colon organoids: from 3D bioprinting to cryopreserved multi-well screening platforms. Toxicol. Vitr. 61, 104606 (2019).
Baptista, P. M. et al. The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology 53, 604–617 (2011).
Giobbe, G. G. et al. Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture. Nat. Commun. 10, 5658 (2019).
Dye, B. R. et al. In vitro generation of human pluripotent stem cell derived lung organoids. eLife 4, e05098 (2015).
Zhu, Y. et al. A hollow fiber system for simple generation of human brain organoids. Integr. Biol. 9, 774–781 (2017).
Geuens, T. et al. Thiol-ene cross-linked alginate hydrogel encapsulation modulates the extracellular matrix of kidney organoids by reducing abnormal type 1a1 collagen deposition. Biomaterials 275, 120976 (2021).
Gupta, A. K. et al. Scaffolding kidney organoids on silk. J. Tissue Eng. Regen. Med. 13, 812–822 (2019).
Curvello, R. et al. Engineered plant-based nanocellulose hydrogel for small intestinal organoid growth. Adv. Sci. 8, 2002135 (2020).
Krüger, M. et al. Cellulose nanofibril hydrogel promotes hepatic differentiation of human liver organoids. Adv. Healthc. Mater. 9, e1901658 (2020).
Nowak, M., Freudenberg, U., Tsurkan, M. V., Werner, C. & Levental, K. R. Modular GAG-matrices to promote mammary epithelial morphogenesis in vitro. Biomaterials 112, 20–30 (2017).
Ma, Z. et al. Self-organizing human cardiac microchambers mediated by geometric confinement. Nat. Commun. 6, 7413 (2015).
Sorrentino, G. et al. Mechano-modulatory synthetic niches for liver organoid derivation. Nat. Commun. 11, 3416 (2020).
Greggio, C. et al. Artificial three-dimensional niches deconstruct pancreas development in vitro. Development 140, 4452–4462 (2013).
Hainline, K. M. et al. Self-assembling peptide gels for 3D prostate cancer spheroid culture. Macromol. Biosci. 19, 1800249 (2019).
Fumagalli, A. et al. Plasticity of Lgr5-negative cancer cells drives metastasis in colorectal cancer. Cell Stem Cell 26, 569–578.e7 (2020).
Ylä-Outinen, L., Joki, T., Varjola, M., Skottman, H. & Narkilahti, S. Three-dimensional growth matrix for human embryonic stem cell-derived neuronal cells. J. Tissue Eng. Regen. Med. 8, 186–194 (2014).
Lancaster, M. A. et al. Guided self-organization and cortical plate formation in human brain organoids. Nat. Biotechnol. 35, 659–666 (2017).
Dye, B. R. et al. A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids. eLife 5, e19732 (2016).
Nayak, B., Balachander, G. M., Manjunath, S., Rangarajan, A. & Chatterjee, K. Tissue mimetic 3D scaffold for breast tumor-derived organoid culture toward personalized chemotherapy. Colloids Surf. B 180, 334–343 (2019).
Garreta, E. et al. Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells. Nat. Mater. 18, 397–405 (2019).
Ye, S. et al. A chemically defined hydrogel for human liver organoid culture. Adv. Funct. Mater. 30, 2000893 (2020).
Barretina, J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603–607 (2012).
Gillet, J. P., Varma, S. & Gottesman, M. M. The clinical relevance of cancer cell lines. J. Natl Cancer Inst. 105, 452–458 (2013).
Lai, Y. et al. Current status and perspectives of patient-derived xenograft models in cancer research. J. Hematol. Oncol. 10, 106 (2017).
Day, C. P., Merlino, G. & Van Dyke, T. Preclinical mouse cancer models: a maze of opportunities and challenges. Cell 163, 39–53 (2015).
Ben-David, U. et al. Patient-derived xenografts undergo mouse-specific tumor evolution. Nat. Genet. 49, 1567–1575 (2017).
Wong, C. H., Siah, K. W. & Lo, A. W. Estimation of clinical trial success rates and related parameters. Biostatistics 20, 273–286 (2019).
Matano, M. et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat. Med. 21, 256–262 (2015).
Zafra, M. P. et al. Optimized base editors enable efficient editing in cells, organoids and mice. Nat. Biotechnol. 36, 888–896 (2018).
Artegiani, B. et al. Fast and efficient generation of knock-in human organoids using homology-independent CRISPR–Cas9 precision genome editing. Nat. Cell Biol. 22, 321–331 (2020).
Acknowledgements
We thank T. M. Lozanoski, J. G. Roth and R. E. Dewi for insightful conversations and editing of the manuscript. B.L.L. acknowledges financial support from the Stanford Bio-X Bowes Graduate Fellowship. R.A.S. acknowledges financial support from the National Institutes of Health Training Grant in Biotechnology (T32-GM008412) and the Stanford Lieberman Fellowship. This work was supported by funding from the National Institutes of Health (R01 EB027171, U01 DK085527) and the National Science Foundation (NSF CBET 2033302). The work of the Lutolf laboratory in the area of cancer organoid biology and technology is supported by the Personalized Health and Related Technologies Initiative from the ETH Board, the Swiss 3R Competence Centre (https://swiss3rcc.org) and the École Polytechnique Fédérale de Lausanne (EPFL).
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B.L.L. and S.C.H. conceived the Review. B.L.L. wrote the Review. R.A.S., B.L.L. and N.B. conceived and illustrated the figures and table. B.L.L., R.A.S., N.B., M.P.L. and S.C.H. edited the Review. All authors read and approved the final manuscript contents.
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LeSavage, B.L., Suhar, R.A., Broguiere, N. et al. Next-generation cancer organoids. Nat. Mater. 21, 143–159 (2022). https://doi.org/10.1038/s41563-021-01057-5
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DOI: https://doi.org/10.1038/s41563-021-01057-5
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