Chinese experts consensus on quality control standards for tumor organoids diagnosis and treatment platform (2022 version)

doi:10.19401/j.cnki.1007-3639.2022.07.010

Abstract

Abstract:

Recently, advances in organoid technology have opened new avenues for the development of novel models of human cancer. Patient-derived tumor organoids retain phenotypes such as histopathological, genetic and molecular features of the original tumor. The generation of cancer, more closer to the real pathophysiological status organoids from primary patient material enables a range of therapeutic agents to be tested in the resulting organoid cultures that not only can be an excellent and innovative platform for drug discovery, but also through sensitivity test of the drug candidates can predict patient response to therapy, thereby holding great promise for personalized medicine. However, compared to traditional biobanks, living biobanks from patient-derived organoids requires stricter quality control and higher level of technical standards. With further research of organoids, a variety of solid tumors have been covered. Organoid technology was named technology of the year in life sciences in 2017. There is no quality control standard for the construction, identification and drug-screening applications of patient-derived cancer organoids in China, and there is also a lack of experts consensus for drug sensitivity test to guide precise tumor treatment. Therefore, based on the advances of patient-derived tumor organoids at home and abroad in the precision medicine, the Multidisciplinary Diagnosis and Treatment Professional Committee of China Anti-cancer Association and the Tumor Endocrinology Professional Committee of China Anti-cancer Association have formulated “Chinese experts consensus on quality control standards for tumor organoids diagnosis and treatment platform (2022 version)”, which improves the understanding of Chinese clinicians and medical researchers on organoids’ drug sensitivity test, standardizes the quality of tumor organoids diagnosis and treatment platform, and guide its clinical application in the domestic precision medicine. This consensus will be regularly updated based on the further research on organoids.

Key words: Organoids, Diagnosis and treatment platform, Quality control, Consensus, Tumor

CLC Number:

R73-3

The Society of Cancer Multidisciplinary Diagnosis and Treatment, China Anti-Cancer Association, The Society of Cancer Endocrinology, China Anti-Cancer Association. Chinese experts consensus on quality control standards for tumor organoids diagnosis and treatment platform (2022 version)[J]. China Oncology, 2022, 32(7): 657-668.

References 80

[1]	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
[2]	BALANI S, NGUYEN L V, EAVES C J. Modeling the process of human tumorigenesis[J]. Nat Commun, 2017, 8: 15422. doi: 10.1038/ncomms15422
[3]	BEN-DAVID U, HA G, TSENG Y Y, et al. Patient-derived xenografts undergo mouse-specific tumor evolution[J]. Nat Genet, 2017, 49(11): 1567-1575. doi: 10.1038/ng.3967
[4]	BYRNE A T, ALFEREZ D G, AMANT F, et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts[J]. Nat Rev Cancer, 2017, 17(4): 254-268. doi: 10.1038/nrc.2016.140
[5]	DROST J, CLEVERS H. Organoids in cancer research[J]. Nat Rev Cancer, 2018, 18(7): 407-418. doi: 10.1038/s41568-018-0007-6
[6]	LI M, IZPISUA BELMONTE J C. Organoids-preclinical models of human disease[J]. N Engl J Med, 2019, 380(6): 569-579. doi: 10.1056/NEJMra1806175
[7]	PUSCHHOF J, PLEGUEZUELOS-MANZANO C, MARTINEZ-SILGADO A, et al. Intestinal organoid cocultures with microbes[J]. Nat Protoc, 2021, 16(10): 4633-4649. doi: 10.1038/s41596-021-00589-z
[8]	SUGIMOTO S, KOBAYASHI E, FUJII M, et al. An organoid-based organ-repurposing approach to treat short bowel syndrome[J]. Nature, 2021, 592(7852): 99-104.
[9]	HENDRIKS D, ARTEGIANI B, HU H L, et al. Establishment of human fetal hepatocyte organoids and CRISPR-Cas9-based gene knockin and knockout in organoid cultures from human liver[J]. Nat Protoc, 2021, 16(1): 182-217. doi: 10.1038/s41596-020-00411-2
[10]	ROCK J R, ONAITIS M W, RAWLINS E L, et al. Basal cells as stem cells of the mouse trachea and human airway epithelium[J]. Proc Natl Acad Sci USA, 2009, 106(31): 12771-12775. doi: 10.1073/pnas.0906850106
[11]	VAN DE WETERING M, FRANCIES H E, FRANCIS J M, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients[J]. Cell, 2015, 161(4): 933-945. doi: 10.1016/j.cell.2015.03.053
[12]	FUJII M, SHIMOKAWA M, DATE S, et al. A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis[J]. Cell Stem Cell, 2016, 18(6): 827-838. doi: 10.1016/j.stem.2016.04.003
[13]	WEEBER F, VAN DE WETERING M, HOOGSTRAAT M, et al. Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases[J]. Proc Natl Acad Sci USA, 2015, 112(43): 13308-13311. doi: 10.1073/pnas.1516689112
[14]	BOJ S F, HWANG C I, BAKER L A, et al. Organoid models of human and mouse ductal pancreatic cancer[J]. Cell, 2015, 160(1/2): 324-338. doi: 10.1016/j.cell.2014.12.021
[15]	BARTFELD S, BAYRAM T, VAN DE WETERING M, et al. In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection[J]. Gastroenterology, 2015, 148(1): 126-136.e6. doi: 10.1053/j.gastro.2014.09.042
[16]	BROUTIER L, MASTROGIOVANNI G, VERSTEGEN M M, et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening[J]. Nat Med, 2017, 23(12): 1424-1435. doi: 10.1038/nm.4438
[17]	SACHS N, DE LIGT J, KOPPER O, et al. A living biobank of breast cancer organoids captures disease heterogeneity[J]. Cell, 2018, 172(1/2): 373-386.e10. doi: 10.1016/j.cell.2017.11.010
[18]	GAO D, VELA I, SBONER A, et al. Organoid cultures derived from patients with advanced prostate cancer[J]. Cell, 2014, 159(1): 176-187. doi: 10.1016/j.cell.2014.08.016
[19]	DRIEHUIS E, KRETZSCHMAR K, CLEVERS H. Establishment of patient-derived cancer organoids for drug-screening applications[J]. Nat Protoc, 2020, 15(10): 3380-3409. doi: 10.1038/s41596-020-0379-4
[20]	OOFT S N, WEEBER F, DIJKSTRA K K, et al. Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients[J]. Sci Transl Med, 2019, 11(513): eaay2574.
[21]	VLACHOGIANNIS G, HEDAYAT S, VATSIOU A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers[J]. Science, 2018, 359(6378): 920-926. doi: 10.1126/science.aao2774
[22]	SEPPÄLÄ T T, ZIMMERMAN J W, SURI R, et al. Precision medicine in pancreatic cancer: patient derived organoid pharmacotyping is a predictive biomarker of clinical treatment response[J]. Clin Cancer Res, 2022: 4165.
[23]	CHEN P, ZHANG X, DING R B, et al. Patient-derived organoids can guide personalized-therapies for patients with advanced breast cancer[J]. Adv Sci (Weinh), 2021, 8(22): e2101176.
[24]	YAO Y, XU X Y, YANG L F, et al. Patient-derived organoids predict chemoradiation responses of locally advanced rectal cancer[J]. Cell Stem Cell, 2020, 26(1): 17-26.e6. doi: 10.1016/j.stem.2019.10.010
[25]	NOZAKI K, MOCHIZUKI W, MATSUMOTO Y, et al. Co-culture with intestinal epithelial organoids allows efficient expansion and motility analysis of intraepithelial lymphocytes[J]. J Gastroenterol, 2016, 51(3): 206-213. doi: 10.1007/s00535-016-1170-8
[26]	CATTANEO C M, DIJKSTRA K K, FANCHI L F, et al. Tumor organoid-T-cell coculture systems[J]. Nat Protoc, 2020, 15(1): 15-39. doi: 10.1038/s41596-019-0232-9
[27]	PAULI C, HOPKINS B D, PRANDI D, et al. Personalized in vitro and in vivo cancer models to guide precision medicine[J]. Cancer Discov, 2017, 7(5): 462-477. doi: 10.1158/2159-8290.CD-16-1154
[28]	KOPPER O, DE WITTE C J, LÕHMUSSAAR K, et al. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity[J]. Nat Med, 2019, 25(5): 838-849. doi: 10.1038/s41591-019-0422-6
[29]	LINKOUS A, BALAMATSIAS D, SNUDERL M, et al. Modeling patient-derived glioblastoma with cerebral organoids[J]. Cell Rep, 2019, 26(12): 3203-3211.e5. doi: 10.1016/j.celrep.2019.02.063
[30]	UBINK I, BOLHAQUEIRO A C F, ELIAS S G, et al. Organoids from colorectal peritoneal metastases as a platform for improving hyperthermic intraperitoneal chemotherapy[J]. Br J Surg, 2019, 106(10): 1404-1414. doi: 10.1002/bjs.11206
[31]	CHEN H, GOTIMER K, DE SOUZA C, et al. Short-term organoid culture for drug sensitivity testing of high-grade serous carcinoma[J]. Gynecol Oncol, 2020, 157(3): 783-792. doi: 10.1016/j.ygyno.2020.03.026
[32]	DRIEHUIS E, KOLDERS S, SPELIER S, et al. Oral mucosal organoids as a potential platform for personalized cancer therapy[J]. Cancer Discov, 2019, 9(7): 852-871. doi: 10.1158/2159-8290.CD-18-1522
[33]	LÕHMUSSAAR K, OKA R, ESPEJO VALLE-INCLAN J, et al. Patient-derived organoids model cervical tissue dynamics and viral oncogenesis in cervical cancer[J]. Cell Stem Cell, 2021, 28(8): 1380-1396.e6. doi: 10.1016/j.stem.2021.03.012
[34]	DROST J, KARTHAUS W R, GAO D, et al. Organoid culture systems for prostate epithelial and cancer tissue[J]. Nat Protoc, 2016, 11(2): 347-358. doi: 10.1038/nprot.2016.006
[35]	MARSEE A, ROOS F J M, VERSTEGEN M M A, et al. Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids[J]. Cell Stem Cell, 2021, 28(5): 816-832. doi: 10.1016/j.stem.2021.04.005
[36]	VOTANOPOULOS K I, FORSYTHE S, SIVAKUMAR H, et al. Model of patient-specific immune-enhanced organoids for immunotherapy screening: feasibility study[J]. Ann Surg Oncol, 2020, 27(6): 1956-1967. doi: 10.1245/s10434-019-08143-8
[37]	OU L L, WANG H S, HUANG H, et al. Preclinical platforms to study therapeutic efficacy of human γδ T cells[J]. Clin Transl Med, 2022, 12(6): e814.
[38]	MAGILL S T, VASUDEVAN H N, SEO K, et al. Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma[J]. Nat Commun, 2020, 11(1): 4803.
[39]	NYS C, LEE Y L, ROOSE H, et al. Exploring stem cell biology in pituitary tumors and derived organoids[J]. Endocr Relat Cancer, 2022, 29(7): 427-450. doi: 10.1530/ERC-21-0374
[40]	WENSINK G E, ELIAS S G, MULLENDERS J, et al. Patient-derived organoids as a predictive biomarker for treatment response in cancer patients[J]. NPJ Precis Oncol, 2021, 5(1): 30.
[41]	BANDA M, MCKIM K L, MYERS M B, et al. Outgrowth of erlotinib-resistant subpopulations recapitulated in patient-derived lung tumor spheroids and organoids[J]. PLoS One, 2020, 15(9): e0238862.
[42]	DE WITTE C J, ESPEJO VALLE-INCLAN J, HAMI N, et al. Patient-derived ovarian cancer organoids mimic clinical response and exhibit heterogeneous inter- and intrapatient drug responses[J]. Cell Rep, 2020, 31(11): 107762.
[43]	LEE S H, HU W H, MATULAY J T, et al. Tumor evolution and drug response in patient-derived organoid models of bladder cancer[J]. Cell, 2018, 173(2): 515-528.e17. doi: 10.1016/j.cell.2018.03.017
[44]	SHARICK J T, WALSH C M, SPRACKLING C M, et al. Metabolic heterogeneity in patient tumor-derived organoids by primary site and drug treatment[J]. Front Oncol, 2020, 10: 553. doi: 10.3389/fonc.2020.00553
[45]	UKAI S, HONMA R, SAKAMOTO N, et al. Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS3 contributes to the attainment of features of cancer stem cell[J]. Oncogene, 2020, 39(50): 7265-7278. doi: 10.1038/s41388-020-01492-9
[46]	DRAIN A P, ZAHIR N, NORTHEY J J, et al. Matrix compliance permits NF-κB activation to drive therapy resistance in breast cancer[J]. J Exp Med, 2021, 218(5): e20191360.
[47]	CHEN B S, ALVARADO D M, ITICOVICI M, et al. Interferon-induced IDO1 mediates radiation resistance and is a therapeutic target in colorectal cancer[J]. Cancer Immunol Res, 2020, 8(4): 451-464. doi: 10.1158/2326-6066.CIR-19-0282
[48]	PUCA L, BAREJA R, PRANDI D, et al. Patient derived organoids to model rare prostate cancer phenotypes[J]. Nat Commun, 2018, 9(1): 2404.
[49]	BOLLINGER J, MAY E, MATHEWS D, et al. Patients’ perspectives on the derivation and use of organoids[J]. Stem Cell Reports, 2021, 16(8): 1874-1883. doi: 10.1016/j.stemcr.2021.07.004
[50]	BREDENOORD A L, CLEVERS H, KNOBLICH J A. Human tissues in a dish: the research and ethical implications of organoid technology[J]. Science, 2017, 355(6322): eaaf9414.
[51]	BOERS S N, VAN DELDEN J J M, BREDENOORD A L. Broad consent is consent for governance[J]. Am J Bioeth, 2015, 15(9): 53-55.
[52]	SCHUTGENS F, CLEVERS H. Human organoids: tools for understanding biology and treating diseases[J]. Annu Rev Pathol, 2020, 15: 211-234. doi: 10.1146/annurev-pathmechdis-012419-032611
[53]	BOERS S N, VAN DELDEN J J, CLEVERS H, et al. Organoid biobanking: identifying the ethics: organoids revive old and raise new ethical challenges for basic research and therapeutic use[J]. EMBO Rep, 2016, 17(7): 938-941. doi: 10.15252/embr.201642613
[54]	BALLARD D, BOYER C, ALEXANDER J. Organoids-preclinical models of human disease[J]. N Engl J Med, 2019, 380(20): 1981-1982. doi: 10.1056/NEJMc1903253
[55]	CHALABI M, FANCHI L F, DIJKSTRA K K, et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers[J]. Nat Med, 2020, 26(4): 566-576. doi: 10.1038/s41591-020-0805-8
[56]	NARASIMHAN V, WRIGHT J A, CHURCHILL M, et al. Medium-throughput drug screening of patient-derived organoids from colorectal peritoneal metastases to direct personalized therapy[J]. Clin Cancer Res, 2020, 26(14): 3662-3670. doi: 10.1158/1078-0432.CCR-20-0073
[57]	STEELE N G, CHAKRABARTI J, WANG J, et al. An organoid-based preclinical model of human gastric cancer[J]. Cell Mol Gastroenterol Hepatol, 2019, 7(1): 161-184. doi: 10.1016/j.jcmgh.2018.09.008
[58]	TIRIAC H, BELLEAU P, ENGLE D D, et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer[J]. Cancer Discov, 2018, 8(9): 1112-1129. doi: 10.1158/2159-8290.CD-18-0349
[59]	LI X D, FRANCIES H E, SECRIER M, et al. Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics[J]. Nat Commun, 2018, 9(1): 2983.
[60]	PHAN N, HONG J J, TOFIG B, et al. A simple high-throughput approach identifies actionable drug sensitivities in patient-derived tumor organoids[J]. Commun Biol, 2019, 2: 78. doi: 10.1038/s42003-019-0305-x
[61]	MAZZOCCHI A R, RAJAN S A P, VOTANOPOULOS K I, et al. In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening[J]. Sci Rep, 2018, 8(1): 2886.
[62]	JACOB F, SALINAS R D, ZHANG D Y, et al. A patient-derived glioblastoma organoid model and biobank recapitulates inter- and intra-tumoral heterogeneity[J]. Cell, 2020, 180(1): 188-204.e22. doi: 10.1016/j.cell.2019.11.036
[63]	WANG T, PAN W J, ZHENG H, et al. Accuracy of using a patient-derived tumor organoid culture model to predict the response to chemotherapy regimens in stage Ⅳ colorectal cancer: a blinded study[J]. Dis Colon Rectum, 2021, 64(7): 833-850. doi: 10.1097/DCR.0000000000001971
[64]	LANCASTER M A, RENNER M, MARTIN C A, et al. Cerebral organoids model human brain development and microcephaly[J]. Nature, 2013, 501(7467): 373-379. doi: 10.1038/nature12517
[65]	NISHINAKAMURA R. Human kidney organoids: progress and remaining challenges[J]. Nat Rev Nephrol, 2019, 15(10): 613-624. doi: 10.1038/s41581-019-0176-x
[66]	LUKONIN I, SERRA D, CHALLET MEYLAN L, et al. Phenotypic landscape of intestinal organoid regeneration[J]. Nature, 2020, 586(7828): 275-280. doi: 10.1038/s41586-020-2776-9
[67]	GANESH K, WU C, O’ROURKE K P, et al. A rectal cancer organoid platform to study individual responses to chemoradiation[J]. Nat Med, 2019, 25(10): 1607-1614. doi: 10.1038/s41591-019-0584-2
[68]	SHI R S, RADULOVICH N, NG C, et al. Organoid cultures as preclinical models of non-small cell lung cancer[J]. Clin Cancer Res, 2020, 26(5): 1162-1174. doi: 10.1158/1078-0432.CCR-19-1376
[69]	KIM M, MUN H, SUNG C O, et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening[J]. Nat Commun, 2019, 10(1): 3991.
[70]	ROSENBLUTH J M, SCHACKMANN R C J, GRAY G K, et al. Organoid cultures from normal and cancer-prone human breast tissues preserve complex epithelial lineages[J]. Nat Commun, 2020, 11(1): 1711.
[71]	YAN H H N, SIU H C, LAW S, et al. A comprehensive human gastric cancer organoid biobank captures tumor subtype heterogeneity and enables therapeutic screening[J]. Cell Stem Cell, 2018, 23(6): 882-897.e11. doi: 10.1016/j.stem.2018.09.016
[72]	YAN H H N, SIU H C, HO S L, et al. Organoid cultures of early-onset colorectal cancers reveal distinct and rare genetic profiles[J]. Gut, 2020, 69(12): 2165-2179. doi: 10.1136/gutjnl-2019-320019
[73]	HU H L, GEHART H, ARTEGIANI B, et al. Long-term expansion of functional mouse and human hepatocytes as 3D organoids[J]. Cell, 2018, 175(6): 1591-1606.e19. doi: 10.1016/j.cell.2018.11.013
[74]	SHIOTA J, SAMUELSON L C, RAZUMILAVA N. Hepatobiliary organoids and their applications for studies of liver health and disease: are we there yet?[J]. Hepatology, 2021, 74(4): 2251-2263. doi: 10.1002/hep.31772
[75]	YUN J, LEE S H, KIM S Y, et al. Antitumor activity of amivantamab (JNJ-61186372), an EGFR-MET bispecific antibody, in diverse models of EGFR exon 20 insertion-driven NSCLC[J]. Cancer Discov, 2020, 10(8): 1194-1209. doi: 10.1158/2159-8290.CD-20-0116
[76]	WANG Y, JIANG T, QIN Z, et al. HER2 exon 20 insertions in non-small cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib[J]. Ann Oncol, 2019, 30(3): 447-455. doi: 10.1093/annonc/mdy542
[77]	DEKKERS J F, VAN VLIET E J, SACHS N, et al. Long-term culture, genetic manipulation and xenotransplantation of human normal and breast cancer organoids[J]. Nat Protoc, 2021, 16(4): 1936-1965. doi: 10.1038/s41596-020-00474-1
[78]	MAENHOUDT N, DEFRAYE C, BORETTO M, et al. Developing organoids from ovarian cancer as experimental and preclinical models[J]. Stem Cell Reports, 2020, 14(4): 717-729. doi: 10.1016/j.stemcr.2020.03.004
[79]	HU Y W, SUI X Z, SONG F, et al. Lung cancer organoids analyzed on microwell arrays predict drug responses of patients within a week[J]. Nat Commun, 2021, 12(1): 2581. doi: 10.1038/s41467-021-22676-1
[80]	WANG Y C, JEON H. 3D cell cultures toward quantitative high-throughput drug screening[J]. Trends Pharmacol Sci, 2022, 43(7): 569-581. doi: 10.1016/j.tips.2022.03.014