Table 1.
Summary of study characteristics and main results.
| Study | Cancer type | Organoid establishment success rate (%) | # of organoid lines used for treatment experiments | Multiple organoid lines per patient | Matched healthy tissue organoids | Standard-of-care testing | Clinical comparison | Drug screen | Outcomes regarding prediction of clinical treatment response | |
|---|---|---|---|---|---|---|---|---|---|---|
| Gastro-intestinal cancer | ||||||||||
| van de Wetering M. et al. (2) | Colorectal cancer | 90% | 19 | Drug screen on organoids. No clinical comparison. | ||||||
| Koppens M. et al. (8) | Colon cancer | not reported | 2 | Efficacy of EZH2 inhibition in organoids. No clinical comparison. | ||||||
| Verissimo CS. et al. (9) | RAS mutant colorectal cancer | n.a. | 2 | Organoid response towards EGFR-RAS-ERK targeting in relation to KRAS mutation status. No clinical comparison. | ||||||
| Buzzelli JN. et al. (10) | Colorectal cancer liver metastases | 76.5% | 3 | Efficacy of standard-of-care chemotherapy in organoids. No clinical comparison. | ||||||
| Vlachogiannis G. et al. (11) | Metastatic gastrointestinal tumors | not reported | 21 | Sensitivity 100%, specificity 93%, PPV 88%, NPV 100% for organoids in forecasting clinical response to targeted agents or chemotherapeutics. | ||||||
| Gao M. et al. (12) | Gastric cancer | not reported | 2 (from 1 patient) | Testing of standard-of-care chemotherapeutics. Descriptive clinical comparison (N=1) showed lowest IC50 value for 5-FU (out of 4 chemotherapeutics tested) and clinical complete response after 5-FU/RTx treatment. No testing for contribution of RTx to clinical effect. | ||||||
| Li X. et al. (13) | Esophageal adenocarcinoma | 31% | 9 | Drug screen on organoids. Descriptive comparison showing lack of chemotherapy sensitivity in most organoid cultures which resembled the poor clinical response observed. | ||||||
| Yan HHN. et al. (14) | Gastric cancer | 50% (cancer), 100% (healthy) | 9 (from 7 patients) | Drug screen on organoids. Descriptive comparison showing lack of organoid response to 5-FU in a patient that showed progressive disease upon 5-FU. Two other patients showed a clinical response to 5-FU/cisplatin which was resembled in the organoids. | ||||||
| Votanopoulos KI. et al. (15) | Appendiceal cancer | 75% | 9 | Chemosensitivity testing of organoids. No clinical comparison. | ||||||
| Li J. et al. (16) | Gastric cancer (ascites-derived) | 92% | 7 | Drug screening of organoids. No clinical comparison. | ||||||
| Schumacher D. et al. (17) | Colorectal cancer | not reported | 38 | Efficacy of EGFR-targeted therapy and its downstream targets (MEK and mTOR) in relation to KRAS mutation status in organoids. No clinical comparison. | ||||||
| Seidlitz T. et al. (18) | Gastric cancer | not reported | 4 | Drug testing of organoids (targeting HER2, c-KIT or CDK4/6). No clinical comparison. | ||||||
| Ubink I. et al. (19) | Colorectal peritoneal metastases | Not reported | 5 | Sensitivity to HIPEC chemotherapy and efficacy of addition of ATR inhibitor. No clinical comparison. | ||||||
| Pasch CA. et al. (20) | Multiple types of cancer (treatment only on (m)CRC) | 76% | 5 | Descriptive clinical comparison (N=1). Clinical response to FOLFOX in a patient of which the organoid showed an intermediate response towards 5-FU/oxaliplatin treatment. | ||||||
| Steele NG. et al. (21) | Gastric cancer | not reported | 6 | Drug screening of organoids. Descriptive clinical comparison (N=2) showing a similar response in the organoid for one patient but not in the other. | ||||||
| Ganesh K. et al. (22) | Rectal cancer | 77% | 21 | Drug screening of organoids. Clinical comparison for chemotherapy (N=7) showing a correlation of AUC for both 5-FU and FOLFOX with progression-free survival of the corresponding patient (r=0.86, p=0.024). Descriptive comparison of radiosensitivity (N=7) showing organoid responds corresponds with clinical radiotherapy response. | ||||||
| Ooft SN. et al. (23) | Metastatic colorectal cancer | 63% | Varies per treatment | Prediction of response to irinotecan monotherapy (N=10): accuracy of classifier 80%. Prediction of response to 5-FU/irinotecan combination therapy (N=12): 83.3% correctly classified. Prediction of response to 5-FU-oxaliplatin (N=16): no correlation with clinical response. | ||||||
| Costales-Carrera A. et al. (24) | Colon cancer | not reported | 3 | Efficacy of plocabulin in organoids. No clinical comparison. | ||||||
| Yao Y. et al. (25) | Locally advanced rectal cancer | 85.7% | 80 | High correlation between organoid response and clinical outcomes for prediction of neoadjuvant chemoradiation efficacy: AUC 88.20% (76.46-98.67%), accuracy 84.43% (72.40-93.75%), sensitivity 78.01% (55.56-95%), specificity 91.97% (77.78-100%). | ||||||
| Narasimhan V. et al. (26) | Colorectal peritoneal metastases | 68% | 15 | Drug screening of organoids. Descriptive clinical comparison (N=3) in which drug treatment was selected based on organoid sensitivity which was successful for 1 patient. | ||||||
| Zerp SF. et al. (27) | Colorectal cancer | not reported | 3 | Efficacy of APG-880 as a radiosensitizer in organoids. No clinical comparison. | ||||||
| Derouet MF. et al. (28) | Esophageal adenocarcinoma | 57.2% | 16 | Descriptive clinical comparison (N=4) showing an overlap between the organoid and tumor response. | ||||||
| Arena S. et al. (29) | Colorectal cancer | not reported | 5 | Drug testing on organoids. Descriptive clinical comparison (N=3) which corresponded with organoid sensitivity. | ||||||
| Abdominal (non-GI tract) cancer | ||||||||||
| Huang L. et al. (30) | Pancreatic cancer | not reported | 5 | Drug screen of organoids. No clinical comparison. | ||||||
| Broutier L. et al. (31) | Liver cancer | 44% | 6 | Drug sensitivity testing of organoids. No clinical comparison. | ||||||
| Nuciforo S. et al. (32) | Hepatocellular carcinoma | 26% | 12 | Efficacy of sorafenib on organoids. No clinical comparison. | ||||||
| Tiriac ML. 2018 (33) | Pancreatic cancer | 75% | 66 | Descriptive comparison of organoid response towards clinical response. For one patient retrospective clinical data paralleled the chemosensitivity profile of the organoid. | ||||||
| Li L. et al. (34) | Liver cancer | not reported | 27 (from 5 patients) | Drug screen of organoids. No clinical comparison. | ||||||
| Hennig A. et al. (35) | Pancreatic cancer | 71% | 10 | Efficacy of standard-of-care chemotherapy stratified for KRT81 status. No clinical comparison. | ||||||
| Bian B. et al. (36) | Pancreatic cancer | not reported | 24 | Efficacy of BET-inhibitor treatment on organoids. No clinical comparison. | ||||||
| Driehuis E. et al. (37) | Pancreatic cancer | 62% | 24 | Drug screen on organoids. Descriptive comparison towards clinical response (N=4) showing an overall correlation between organoid and clinical response. | ||||||
| Ponz-Sarvise M. et al. (38) | Pancreatic cancer | not reported | 2 | Drug sensitivity testing of organoids. No clinical comparison. | ||||||
| Castven D. et al. (39) | Liver cancer | 11% | 5 | Testing efficacy of targeted agents based on mutational variants in organoids. No clinical comparison. | ||||||
| Sharick JT. et al. (40) | Pancreatic and Breast cancer | 64% (for pancreatic cancer), 54% (for breast cancer) | 7 (pancreas), 11 (breast) | Using metabolic heterogeneity to predict treatment response in pancreatic cancer organoids (N=7). Three patients were classified as predicted non-responders and all showed tumor recurrence within one year whereas four patients that were classified as predicted responders all remained free of tumor recurrence for more than one year. | ||||||
| Seppälä TT. et al. (41) | Pancreatic cancer | 77% | 13 | Pharmacotyping of organoids. No clinical comparison. | ||||||
| Saltsman J. et al. (42) | Hepatoblastoma | not reported | 1 | Drug testing on normal liver and tumor organoid from one patient. No clinical comparison. | ||||||
| Liu J. et al. (24) | Liver cancer | not reported | 4 | Effect of co-culture system with cancer-associated fibroblasts on drug sensitivity in organoids. No clinical comparison. | ||||||
| Urogenital and gynecological cancer | ||||||||||
| Gao D. et al., 2014 (43) | Metastatic prostate cancer or CTCs | 15-20% | 6 | Sensitivity to androgen receptor and PI3K inhibitors in organoids. No clinical comparison. | ||||||
| Girda E. et al. (44) | Endometrial cancer | 100% | 14 (varies per drug) | Drug testing on organoids. No clinical comparison. | ||||||
| Lee SH. et al. (45) | Bladder cancer | 70% | 11 | Drug screen of organoids and comparison to in vivo (mice) response. No clinical comparison. | ||||||
| Puca L. et al. (46) | Prostate cancer | 16% | 6 | Drug screening on organoids. No clinical comparison. | ||||||
| Kopper O. et al. (47) | Ovarian cancer | 65% | 21 | Descriptive clinical comparison: organoids derived from clinical resistant recurrent disease were more resistant compared to the clinically sensitive primary disease counterpart (N=1). Drug screen of organoids and comparison to in vivo (mice) response. | ||||||
| Boretto M. et al. (48) | Endometrial cancer | 20% | 5 | Drug response to standard-of-care chemotherapeutics. No clinical comparison. | ||||||
| Mullenders J. et al. (49) | Bladder cancer | 57.9% | 3 | Drug response to standard-of-care chemotherapeutics. No clinical comparison. | ||||||
| Calandrini C. et al. (50) | Childhood kidney cancer | 100% for healthy tissue, 75% for Wilms tumor, 100% for MRTK, 75% for RCC. Unsuccessful for rare kidney tumor types | 4 | Drug screen of cancer and healthy tissue organoids. No clinical comparison. | ||||||
| de Witte C.J. et al. (51) | Ovarian cancer | not reported | 36 | Drug screening on organoids. Organoid drug response to carboplatin+paclitaxel treatment showed significant correlation with clinical response (N=7, P<0.01). PDOs generated at interval debulking recapitulated the clinical response to first-line carboplatin and paclitaxel combination treatment for histopathological (p = 5.821e 05), biochemical (p = 0.0004), and radiological (p = 0.0092) outcomes. | ||||||
| Central nervous system cancer | ||||||||||
| Hubert CG. et al. (52) | Glioblastoma | not reported | 1 | Identification of radioresistant cells in organoids. No clinical comparison. | ||||||
| Saengwimol D. et al. (53) | Retinoblastoma | 83% | 1 | Effects of standard-of-care chemotherapeutics. No clinical comparison. | ||||||
| Scognamiglio G. et al. (54) | Chordoma | not reported | 3 | Efficacy study of nivolumab. No clinical comparison. | ||||||
| Loong HF. et al. (55) | Glioblastoma | n.a. | 1 | Prospective identification of everolimus as treatment option using organoids showing subsequent partial clinical response. | ||||||
| Chadwick M. et al. (56) | Glioblastoma | not reported | 4 | Drug screen on organoids. No clinical comparison. | ||||||
| Breast cancer | ||||||||||
| Sachs N. et al. (57) | Breast cancer | >80% | 28 | Drug screening of organoids and comparison to in vivo response in mice. No clinical comparison. | ||||||
| Li X. et al. (58) | Breast cancer | n.a. | 1 | Case-report for drug screening on organoids. No clinical comparison. | ||||||
| Pulmonary cancer | ||||||||||
| Sachs N. 2019 (59) | NSCLC | 28% | 4 | Response to multiple chemotherapeutics and TKI’s. No clinical comparison. | ||||||
| Kim M. et al. (60) | Lung cancer | 87% | 5 | Response to docetaxel, olaparib, erlotinib and crizotinib. No clinical comparison. | ||||||
| Chen J. et al. (61) | NSCLC | not reported | 7 | Response to chemotherapeutics and targeted agents in organoids. No clinical comparison. | ||||||
| Li Z. et al. (62) | NSCLC | 80% | 12 | Drug screen on organoids. No clinical comparison. | ||||||
| Head-and-neck cancer | ||||||||||
| Tanaka N. et al. (63) | Head-and-neck cancer | 37.2% | 4 | Response to cisplatin and docetaxel. No clinical comparison. | ||||||
| Driehuis E. et al. (64) | HNSCC | 65% | 13 | Descriptive comparison of response to radiotherapy (N=7). Organoid response for 6 patients was similar to the observed clinical response. Healthy organoids were not subjected to treatment. | ||||||
| Driehuis E. et al. (65) | HNSCC | n.a. | 8 | Efficacy of EGFR-targeted photodynamic therapy. No clinical comparison. | ||||||