organoidmedicine.com

A small copy of one person’s tissue

A patient-derived organoid (PDO) is grown from a biopsy of a person’s own tissue, keeps that person’s genotype and reproduces much of the behaviour of the tissue it came from. The field calls it an avatar, and the clinical question it raises is blunt: if the copy responds to a drug, will the person?7

The most cited attempt at an answer appeared in Science in 2018. A living biobank of organoids from metastatic, heavily pretreated colorectal and gastro-oesophageal cancers — patients already recruited into phase 1/2 trials — showed “a high degree of similarity to the original patient tumors”, and the authors concluded that PDOs “can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs”.1 Eight years of follow-up work has made that sentence more precise rather than louder. A 2026 systematic review and meta-analysis pooled 411 matched patient-model pairs — 267 mouse xenografts and 144 organoids — and put overall concordance between model and patient response at 70%, with organoids performing comparably to xenografts, and with longer progression-free survival among patients whose organoid had responded.7

Seventy per cent is neither a coin toss nor a diagnostic. The distance between promising and proven is where organoid medicine sits today, and this address is a place to say so honestly.

Cystic fibrosis: the clearest case in the field

The story starts in Utrecht in 2013. A team working with intestinal organoids from people with cystic fibrosis found that forskolin — which raises intracellular cAMP and so opens the CFTR channel — makes healthy organoids swell within minutes, while “this effect is strongly reduced in organoids of subjects with cystic fibrosis”. The swelling “corresponds quantitatively with forskolin-induced anion currents in freshly excised ex vivo rectal biopsies”, which turned a genetic defect into a measurement anyone with a microscope could make.8 The assay is known as forskolin-induced swelling, or FIS.

Three papers took it toward the clinic. In 2016, rectal organoids from people carrying “a broad range of CFTR mutations” were exposed to CFTR-modulating drugs, and the in vitro responses “positively correlated with published outcome data from clinical trials”.9 In 2019, organoid responses were compared prospectively with two clinical endpoints in the same individuals — change in lung function and change in sweat chloride — with receiver operating characteristic curves indicating “good-to-excellent accuracy of the organoid-based test for defining clinical responses”.10 And in 2024 the approach was shown to work at continental scale: in the HIT-CF Europe Organoid Study, 502 biopsy procedures on 489 adults across 33 hospitals in 12 countries were shipped to one central laboratory, with a 95% success rate for growing organoids and insufficient sample viability (3.2%) as the main reason for failure.12

Why it matters: the modulator trials were run in people carrying the commonest variants. The trial record for the HIT-CF study puts one variant at “approximately 80% of CF patients” and gating variants at a further 5%, leaving 15% who “represent more than 2000 different rare and mostly uncharacterized CFTR mutations” — too rare, individually, ever to be tested in a conventional trial.14 An organoid offers a way to ask, for one of those individuals, whether an existing modulator does anything at all. That has already been used to support eligibility for compassionate-use treatment in a person with a rare genotype,11 and it is the design principle of the HIT-CF trial that recruited only participants who had completed the organoid study first.14

The regulator’s view is worth reading in full, because it is even-handed. On 16 June 2023 the European Medicines Agency issued a letter of support for the FIS assay as a biomarker of CFTR function, describing it as “performed in patient-derived organoids (PDO) from CF patients’ intestinal stem-cells”, and concluding that “the CHMP supports the development of the FIS assay towards a full validation”. The same letter says that “conclusions on individual level predictions cannot be made based on the presented data”, that “there is no clear consensus on thresholds that define the individual responders or non-responders”, and that “a direct application for prognosis and prediction is considered premature”.13 Encouragement, not qualification.

Reimbursement follows the law rather than the assay. In the Netherlands, where the test was invented, a Dutch health-insurance disputes committee rejected a claim for modulator cover in November 2024 on the ground that the medicine had been designated by the legislator “for patients with the F508del mutation” only.28 The Dutch CF patient association reports a separate binding advice in which an insurer was told to pay for one individual whose benefit “was shown independently by tests, among them on mini-intestines (organoids)”, while noting that the ruling was person-specific.29 There is, in other words, no country in which a swelling organoid entitles anyone to a prescription; there are individuals for whom it has helped make the case.

Oncology: the largest body of evidence

The oncology strand began with supply. A 2015 Cell paper derived tumour organoid cultures from 20 consecutive colorectal cancer patients, coined the phrase living biobank, and noted that such organoids are “amenable to high-throughput drug screens allowing detection of gene-drug associations”.5 Prediction followed. A 2019 prospective study built an organoid test from metastatic lesions in colorectal cancer specifically to identify non-responders; it “predicted response of the biopsied lesion in more than 80% of patients” on one chemotherapy backbone “without misclassifying patients who would have benefited”, and — the part worth remembering — “failed to predict outcome” for a different combination.2 A test can be informative for one regimen and useless for the next.

In pancreatic cancer, a 2018 organoid library reproduced “the mutational spectrum and transcriptional subtypes of primary pancreatic cancer”, showed heterogeneous drug responses, and yielded “organoid-based gene expression signatures of chemosensitivity”; the patient comparison in that paper was made, in its own words, “in a case study manner”.3 In locally advanced rectal cancer, organoids from patients enrolled in a phase III trial of neoadjuvant chemoradiation matched the patients’ own responses with “84.43% accuracy, 78.01% sensitivity, and 91.97% specificity”, leading the authors to suggest organoids “may represent a companion diagnostic tool” — a proposal, not a status.4

What prospective trials show, and what they do not

The honest counterweight is the SENSOR trial, published in 2021. It was single-arm and prospective, and it set out to allocate patients with metastatic colorectal cancer to off-label or investigational drugs on the strength of their organoids. Of 61 patients included, organoids grew for 31 of 54 eligible; 25 cultures were screened; 19 responded to something in the panel; six patients were actually treated; and “patients did not demonstrate objective clinical responses to the recommended treatment”. The authors named the failure points precisely: “the culture success rate, clinical deterioration of patients during standard of care, and rational design of drug panels”.6

Every one of those is still a live constraint.

• Take rate. Organoids do not always grow. Rectal biopsies in cystic fibrosis reach 95%;12 tumours are far less reliable, to the point that an ongoing multicentre precision-oncology programme restricts one of its phase 2 strata to cancers with a PDO take-on rate of 50% or better.15
• Turnaround. A standard protocol puts establishment plus screening “within 3 months”, depending on the starting material and the number of therapies tested.16 For a person progressing on treatment, three months can be the whole window.
• Missing compartments. Conventional tumour organoids “typically contain exclusively neoplastic epithelium and require artificial reconstitution to recapitulate the tumor microenvironment” — no stroma, no vasculature, no immune system. An air-liquid interface method that preserves native T, B, NK and myeloid cells inside the organoid was developed precisely to model checkpoint blockade, which plain epithelial cultures cannot.17
• Representativeness and speed as a set. A 2024 review lists the obstacles to clinical implementation as “representativeness, success rate, assay speed, and lack of a tumor microenvironment”, with co-culture work under way against them.18

None of this makes organoids a dead end; it makes them a tool with a specification. Reviews of human organoids as model systems put the same point positively: they “provide unique opportunities for the study of human disease and complement animal models”.19

When the organoid is the treatment

A second clinical strand does not test anything. In July 2022 a team in Tokyo reported the first transplantation of an organoid into a person: healthy colonic mucosa taken from the patient’s own bowel, cultured for about a month into spheres 0.1 to 0.2 mm across, and delivered back into that same patient’s colon by colonoscopy, with examinations at 4 and 8 weeks and follow-up planned for a year and for up to eight patients in all. Because the cells are the patient’s own, the report notes, rejection does not arise.20

In the liver, cholangiocyte organoids were shown in Science in 2021 to repair human bile ducts in donor livers kept alive on a perfusion machine outside the body — described by its authors as proof of principle for repairing human biliary epithelium.21 Adjacent to this sits stem-cell-derived islet-cell therapy for type 1 diabetes, infused into the portal vein under immunosuppression in a phase 1-2 study reported in 2025: not an organoid test, but the same underlying idea that a laboratory can build functioning human tissue.22

Regulation and reimbursement, stated plainly

It is worth being exact about what does and does not exist, because the marketing around this field is often ahead of the paperwork.

• No authorised organoid companion diagnostic. The FDA’s public list of authorised companion diagnostic devices contains no organoid-based assay (list checked 24 September 2026).24
• Organoid tests are laboratory developed tests. In the United States such a test is offered by a certified laboratory rather than sold as a kit. The FDA’s May 2024 rule that would have brought these products under device requirements was vacated by a federal district court on 31 March 2025, and on 19 September 2025 the agency reverted the regulation to its earlier text.23
• Drug testing law has moved; the word organoid has not. The FDA Modernization Act 2.0, signed on 29 December 2022, replaced “preclinical tests (including tests on animals)” with “nonclinical tests”, a defined term listing cell-based assays, organ chips and microphysiological systems, computer modelling and animal tests. The statute never says “organoid”.25 The FDA’s April 2025 roadmap does, defining them as “self-organizing cell cultures (e.g. liver organoids, gut organoids) that model native tissue architecture and function” and placing them among the new approach methodologies it intends to validate — for the safety testing of drugs, not for diagnosing anyone.26
• Europe supports development, not prediction. The EMA letter of support is an encouragement to finish validating the FIS assay, and says so.13

The living biobanks behind it

Clinical organoid work rests on collections of living tissue. The Human Cancer Models Initiative, an international collaboration led by the US National Cancer Institute with Cancer Research UK, the Wellcome Sanger Institute and a Dutch organoid foundation, set out to create “up to 1,000 patient-derived next-generation cancer models” — organoids among them — released “as a community resource” with sequencing data distributed through a public genomic data commons.27 Those catalogues, and the consent, provenance and quality records attached to them, are as much a part of organoid medicine as the assay is.5

Who buys a name like OrganoidMedicine.com

The people building in this field are a fair picture of who might want the address:

• Precision-oncology companies running organoid drug-response panels for treating physicians.17
• Clinical and specialist laboratories offering organoid assays as laboratory developed tests.2324
• Hospital networks, expertise centres and trial units that recruit, biopsy and follow the patients.121415
• Contract research organisations running organoid panels for drug developers under the newer nonclinical-testing language.1625
• Biobanks and model catalogues that need a request and provenance portal.527
• Publishers, registries, conferences and patient-facing explainers covering the field for clinicians and families.1329

How the field says it

Papers say personalized medicine,1 precision medicine,6 patient-derived organoid and functional assay.8 Clinicians and patients say the shorter thing: organoid medicine. The phrase covers the whole span above — choosing a drug with a copy of your own tissue, and one day being treated with it — without narrowing to a single assay, tumour type or country.

1. Vlachogiannis G et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.Science, 2018 · PMID 29472484
2. Ooft SN et al. Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients.Science Translational Medicine, 2019 · PMID 31597751
3. Tiriac H et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer.Cancer Discovery, 2018 · PMID 29853643
4. Yao Y et al. Patient-derived organoids predict chemoradiation responses of locally advanced rectal cancer.Cell Stem Cell, 2020 · PMID 31761724
5. van de Wetering M et al. Prospective derivation of a living organoid biobank of colorectal cancer patients.Cell, 2015 · PMID 25957691
6. Ooft SN et al. Prospective experimental treatment of colorectal cancer patients based on organoid drug responses (the SENSOR trial).ESMO Open, 2021 · PMID 33887686
7. Romero JM et al. Comparative analysis of patient-derived organoids and patient-derived xenografts as avatar models for predicting response to anti-cancer therapy.Cancer Treatment Reviews, 2026 · PMID 42497819
8. Dekkers JF et al. A functional CFTR assay using primary cystic fibrosis intestinal organoids.Nature Medicine, 2013 · PMID 23727931
9. Dekkers JF et al. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis.Science Translational Medicine, 2016 · PMID 27334259
10. Berkers G et al. Rectal organoids enable personalized treatment of cystic fibrosis.Cell Reports, 2019 · PMID 30759382
11. Aalbers BL et al. Forskolin induced swelling (FIS) assay in intestinal organoids to guide eligibility for compassionate use treatment in a CF patient with a rare genotype.Journal of Cystic Fibrosis, 2022 · PMID 35110005
12. Bierlaagh MC et al. Centralized intestinal organoid generation is a feasible and safe approach for personalized medicine, as demonstrated in the HIT-CF Europe Organoid Study.Journal of Cystic Fibrosis, 2024 · PMID 38763840
13. Letter of Support for Forskolin-Induced Swelling (FIS) Assay: Biomarker for Cystic Fibrosis Transmembrane Conductance Regulator Protein (CFTR).European Medicines Agency, 16 June 2023 · EMADOC-1700519818-1037383
14. A phase IIb, multicentre, randomised, double-blind, placebo-controlled, crossover study in adults with cystic fibrosis, recruiting from the HIT-CF Organoid Study.ClinicalTrials.gov NCT06468527 · completed June 2025
15. Prospective multicenter study evaluating the feasibility and efficacy of tumor organoid-based precision medicine in patients with advanced refractory cancers.ClinicalTrials.gov NCT05267912 · recruiting, started 2022
16. Driehuis E, Kretzschmar K, Clevers H. Establishment of patient-derived cancer organoids for drug-screening applications.Nature Protocols, 2020 · PMID 32929210
17. Neal JT et al. Organoid modeling of the tumor immune microenvironment.Cell, 2018 · PMID 30550791
18. Thorel L et al. Patient-derived tumor organoids: a new avenue for preclinical research and precision medicine in oncology.Experimental & Molecular Medicine, 2024 · PMID 38945959
19. Kim J, Koo BK, Knoblich JA. Human organoids: model systems for human biology and medicine.Nature Reviews Molecular Cell Biology, 2020 · PMID 32636524
20. World’s first transplantation of an organoid (“mini organ”) into a patient with ulcerative colitis.Tokyo Medical and Dental University, press release, 7 July 2022
21. Sampaziotis F et al. Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.Science, 2021 · PMID 33602855
22. Reichman TW et al. Stem cell-derived, fully differentiated islets for type 1 diabetes.New England Journal of Medicine, 2025 · PMID 40544428
23. Laboratory Developed Tests: the May 2024 final rule, its vacatur on 31 March 2025, and the reverting rule of 19 September 2025.U.S. Food and Drug Administration
24. List of FDA-Authorized Companion Diagnostic Devices (In Vitro and Imaging Tools).U.S. Food and Drug Administration · searched for organoid assays, 24 September 2026
25. Consolidated Appropriations Act, 2023, Public Law 117-328, Section 3209 (Animal testing alternatives): the FDA Modernization Act 2.0.Approved 29 December 2022 · 136 Stat. 5821-5822
26. Roadmap to Reducing Animal Testing in Preclinical Safety Studies.U.S. Food and Drug Administration, April 2025
27. Human Cancer Models Initiative: up to 1,000 patient-derived next-generation cancer models as a community resource.National Cancer Institute, National Institutes of Health
28. Bindend advies SKGZ202302495: modulator cover tied to the genotype designated by the legislator.Geschillencommissie Zorgverzekeringen, 13 November 2024 (Dutch)
29. SKGZ Geschillencommissie geeft patiënt gelijk: an individual case in which organoid test results supported cover.Nederlandse Cystic Fibrosis Stichting, 3 January 2024 (Dutch)