The recent clinical evidence above stands on a decade of landmark work: the first tumor organoid biobanks, the first prospective response-prediction trials, and the perspectives that defined functional precision oncology.
Systematic reviewWensink GE, Elias SG, Mullenders J, et al. · npj Precision Oncology, 2021; 5: 30
A systematic review pooling the published evidence on organoid-based response prediction across tumor types, assessing analytical validity, clinical validity, and clinical utility. Useful as a single entry point into the predictive-biomarker literature this field is built on.
Read the paper →DOI: 10.1038/s41698-021-00168-1
Rectal cancerYao Y, Xu X, Yang L, et al. · Cell Stem Cell, 2020; 26(1): 17–26
A living organoid biobank built alongside a phase III trial in locally advanced rectal cancer. Organoid responses matched patient chemoradiation outcomes with 84% accuracy (78% sensitivity, 92% specificity), supporting organoid testing as a companion tool for treatment stratification.
Read the paper →DOI: 10.1016/j.stem.2019.10.010
GlioblastomaJacob F, Salinas RD, Zhang DY, et al. · Cell, 2020; 180(1): 188–204
Rapidly generated glioblastoma organoids preserving the histology, cellular diversity, expression profiles, and mutational landscape of the parent tumors, extending organoid-based functional testing to the central nervous system.
Read the paper →DOI: 10.1016/j.cell.2019.11.036
Colorectal cancerOoft SN, Weeber F, Dijkstra KK, et al. · Science Translational Medicine, 2019; 11(513): eaay2574
A prospective study showing that organoids generated from metastatic colorectal cancer biopsies predicted response to irinotecan-based chemotherapy in more than 80% of patients, without misclassifying any patient who would have benefited. A template for using organoids to spare non-responders ineffective treatment.
Read the paper →DOI: 10.1126/scitranslmed.aay2574
Rectal cancerGanesh K, Wu C, O’Rourke KP, et al. · Nature Medicine, 2019; 25(10): 1607–1614
Rectal cancer organoids retained the histopathology and genomic alterations of their matched tumors, and their ex vivo responses to chemotherapy and radiation paralleled patients’ progression-free survival: independent confirmation that organoid drug testing tracks clinical outcome.
Read the paper →DOI: 10.1038/s41591-019-0584-2
Ovarian cancerKopper O, de Witte CJ, Lõhmussaar K, et al. · Nature Medicine, 2019; 25(5): 838–849
56 organoid lines from 32 patients covering all main ovarian cancer subtypes, usable for drug screening and capturing subtype-specific responses to platinum chemotherapy, including the emergence of chemoresistance in recurrent disease.
Read the paper →DOI: 10.1038/s41591-019-0422-6
Lung cancerKim M, Mun H, Sung CO, et al. · Nature Communications, 2019; 10: 3991
Lung cancer organoids spanning five histological subtypes that preserved the architecture and genomic alterations of the primary tumors through long-term expansion, and responded to targeted drugs in line with the underlying genotype: subtype-aware screening for the world’s deadliest cancer.
Read the paper →DOI: 10.1038/s41467-019-11867-6
Head & neck cancerDriehuis E, Kolders S, Spelier S, et al. · Cancer Discovery, 2019; 9(7): 852–871
Long-term expandable organoids from head and neck squamous cell carcinoma providing a functional platform for drug and radiotherapy response testing, with organoid responses corresponding to clinical outcome in a retrospective patient series.
Read the paper →DOI: 10.1158/2159-8290.CD-18-1522
PerspectiveTuveson D, Clevers H. · Science, 2019; 364(6444): 952–955
A field-defining perspective from two pioneers of the technology on how self-organizing 3D cultures recapitulate the structure and function of the tissues they model, and what that means for cancer research and drug development.
Read the paper →DOI: 10.1126/science.aaw6985
Prospective trialVlachogiannis G, Hedayat S, Vatsiou A, et al. · Science, 2018; 359(6378): 920–926
Organoids from 110 metastatic biopsies of patients in phase I/II trials mirrored the mutation spectrum and phenotype of the original tumors. Drug responses in the dish forecast responses in the clinic with 100% sensitivity, 93% specificity, 88% positive and 100% negative predictive value: the landmark demonstration that ex vivo organoid testing carries real clinical signal.
Read the paper →DOI: 10.1126/science.aao2774
Pancreatic cancerTiriac H, Belleau P, Engle DD, et al. · Cancer Discovery, 2018; 8(9): 1112–1129
A pancreatic cancer organoid library recapitulating the mutational spectrum and transcriptional subtypes of the primary disease, paired with a drug-testing pipeline (“pharmacotyping”) shown to parallel patient responses to chemotherapy: functional testing in one of the hardest-to-treat solid tumors.
Read the paper →DOI: 10.1158/2159-8290.CD-18-0349
Gastric cancerYan HHN, Siu HC, Law S, et al. · Cell Stem Cell, 2018; 23(6): 882–897
A 63-line biobank from 34 patients spanning normal, dysplastic, primary, and metastatic gastric tissue with whole-exome and transcriptome characterization, in which large-scale drug screening surfaced sensitivities to agents in clinical development.
Read the paper →DOI: 10.1016/j.stem.2018.09.016
Bladder cancerLee SH, Hu W, Matulay JT, et al. · Cell, 2018; 173(2): 515–528
A bladder cancer organoid biobank retaining the mutational heterogeneity of the parental tumors, used to track clonal evolution during treatment and to link drug responses to specific tumor genetics, with responses validated in matched xenografts.
Read the paper →DOI: 10.1016/j.cell.2018.03.017
Breast cancerSachs N, de Ligt J, Kopper O, et al. · Cell, 2018; 172(1–2): 373–386
More than 100 primary and metastatic breast cancer organoid lines reproducing the genetic and pathological diversity of the disease, with organoid drug responses matching tumor subtype biology. Demonstrates that organoid panels can represent patient heterogeneity at scale.
Read the paper →DOI: 10.1016/j.cell.2017.11.010
Prostate cancerBeshiri ML, Tice CM, Tran C, et al. · Clinical Cancer Research, 2018; 24(17): 4332–4345
Organoids derived from advanced, castration-resistant prostate cancers, built explicitly as a therapeutic-screening resource: the models retained the genomic and phenotypic heterogeneity of the disease and supported drug testing across clinically relevant agents.
Read the paper →DOI: 10.1158/1078-0432.CCR-18-0409
Esophageal cancerLi X, Francies HE, Secrier M, et al. · Nature Communications, 2018; 9: 2983
Clinically annotated esophageal adenocarcinoma organoids reproducing the mutations, copy-number changes, and clonal architecture of the primary tumors, with medium-throughput drug sensitivity testing demonstrating their value as a precision-therapeutics screening tool.
Read the paper →DOI: 10.1038/s41467-018-05190-9
ReviewDrost J, Clevers H. · Nature Reviews Cancer, 2018; 18(7): 407–418
The standard review of organoid cancer models: why physiologically relevant 3D human models translate basic research into treatment regimens more efficiently than conventional systems, and where the technology is heading.
Read the paper →DOI: 10.1038/s41568-018-0007-6
Liver cancerBroutier L, Mastrogiovanni G, Verstegen MMA, et al. · Nature Medicine, 2017; 23(12): 1424–1435
Organoids from the major primary liver cancer subtypes retained the histology and molecular features of their tissue of origin even in long-term culture, and drug screening on them surfaced a candidate therapeutic vulnerability: platform utility beyond the colorectal setting.
Read the paper →DOI: 10.1038/nm.4438
PerspectiveLetai A. · Nature Medicine, 2017; 23(9): 1028–1035
The case for functional testing: genomics alone leaves most patients without an actionable match, while directly perturbing living tumor cells with candidate therapies yields decision-grade information. The conceptual backbone of functional precision oncology.
Read the paper →DOI: 10.1038/nm.4389
Colorectal cancervan de Wetering M, Francies HE, Francis JM, et al. · Cell, 2015; 161(4): 933–945
The first tumor organoid biobank: 3D cultures from colorectal cancer resections that maintained the characteristics of the primary tissue and enabled systematic drug screening, laying the methodological foundation for organoid-based precision oncology.
Read the paper →DOI: 10.1016/j.cell.2015.03.053
Prostate cancerGao D, Vela I, Sboner A, et al. · Cell, 2014; 159(1): 176–187
The first organoid lines from metastatic, castration-resistant prostate cancer, recapitulating the molecular diversity of the advanced disease, including subtypes without previous in vitro models, and amenable to drug testing.
Read the paper →DOI: 10.1016/j.cell.2014.08.016