Table 1 Key details and findings of studies on OC PDOs
| Â | Pauli 2017* [67] | Hill 2018 [8] | Phan 2019 [68] | Kopper 2019 [9] | Maru 2019 [69] | Hoffman 2020 [70] | Sun 2020 [71] | Nanki 2020 [72] | Chen 2020 [73] | Maenhoudt 2020 [74] | de Witte 2020 [10] |
|---|---|---|---|---|---|---|---|---|---|---|---|
Patients materials (n of patients) | Fresh Tissue | - Fresh tissue - Pleural effusion | Fresh tissue | Fresh tissue - Pleural effusion - Ascites | Fresh tissue | Fresh tissue | Fresh tissue | Fresh tissue | -Ascites -Pleural effusion | Fresh tissue | - Fresh tissue - Ascites |
Origin of biological material (n of samples) | Ovary | - Omentum (15) - Ovary (12) - Pleural effusion (1) - Mesentery (5) - Diaphragm (1) | - Ovary (1) - Peritoneum (1) | - Ovary (28) - Peritoneum (4) - Omentum (9) - Pleural effusion (2) - Lymph node (1) - Diaphragm (3) - Bowel (1) - Uterus (1) - Abdominal wall (3) - Ascites (4) | NA | - Peritoneum (10) - Omentum (5) | NA | Ovary | Ascites (8) -Pleural effusion (1) | - Omentum (3) - Ovary (3) - Rectum (1) - NA (24) | - Omentum (7) - Ovary/adnexa (19) - Peritoneum (2) - Lymph node (1) - Ascites (3) - Uterus (2) - Abdominal wall (2) |
Clinical setting (n of samples per patient) | NA | - Untreated (10) - NACT (12) - Recurrent (2) | - Untreated (2) - NACT (2) | - Untreated (17) - NACT (9) - Recurrent (7) | NA | - Untreated (12) - NACT (1) | - Untreated (4) - Treated (6) | - Untreated (6)*** - NACT (1)*** | - Untreated (3)*** - Treated (11)*** | - Untreated (9) - NACT (20) - Recurrent (2) | - Untreated (21) - NACT (9) - Recurrent (6) |
Histological types (n) | S (1) | HGS (22) LGS (1) | HGM (1) HGS (1) HGP (1) CS (1) | HGS (2) E (2) HG (2) LGS (14) CC (1) SBT (4) M (5) MBT (7) | E (4) BBT (1) HGS (4) MBT (1) MCB (2) SBT (2) M (1) | HGS (45) | S (10) | HGS (10) CC (10) E (5) MBT (3) Others ** (7) | HGS (5) HGP (1) | HGS (22) LGS (2) MMMT (1) M (1) CC (1) | HGS (11) E (1) HG (2) LGS (4) CC (1) S/MBT (2) M (3) |
Number of patients/number of organoids | 1/1 | 23/33 | 4/4 | 32/56 | 15/9 | 13/15 | 10/10 | 35/28 | 6/14 | 27/12 | 23/36 |
Overall success rate (%) | 100 | 80–90% | 100% | 65% | 60% | 30% | n.s. | 80% | n.s. | 44% | n.s. |
Onset of organoid formation (days) | n.s | 7–14 days | n.s. | 3–14 days | n.s. | n.s. | n.s. | 7–21 days | 3–4 days | n.s. | 20 days |
Expansion | 5 passages | 2 passages | n.s. | 3–31 passages | n.s. | 6–26 passages | n.s. | ≥ 4 passages | n.s. | 1–2 passages | n.s. |
Extracellular matrix | Matrigel | Matrigel | Matrigel or Cultrex BME | Matrigel | Matrigel | Matrigel | Matrigel | Matrigel | Cultrex BME | Matrigel | Matrigel |
Culturing Medium | -Advanced DMEM -Glutamax 1X -B27 −100 U/ml Penicillin −100μg/ml Streptomycin -Primocin 100μg/ml - N-Acetylcysteine 1.25 mM - Mouse Recombinant EGF 50 ng/mL - Human Recombinant FGF-10 20 ng/mL - Recombinant Human FGF-basic 1 ng/mL - Y-27632 10uM - A-83-01500 nM - SB202190 10uM - Nicotinamide 10 mM - PGE2 1uM - Noggin 50 mL - R-Spondin 25 mL | -Advanced DMEM/F12, − 1% penicillin streptomycin- Glutamax 1X -1% HEPES − 100 ng/mL R-spondin 1 -100 ng/mL Noggin −50 ng/mL EGF − 10 ng/mL FGF-10 − 10 ng/mL FGF2 − 1× B27 − 10 mM Nicotinamide − 1.25 mM N-acetylcysteine -1uM Prostaglandin E2 -10uM SB202190 - 500 nm A83–01 | PrEGM medium or Mammocult | - ADF ± 25% conditioned human Wnt3A medium − 25% conditioned human RSPO1 medium − 12 mM HEPES − 1% GlutaMAX − 2% B27 − 1% N2 − 10 ng ml− 1 human EGF − 100 ng ml− 1 human noggin − 100 ng ml− 1 human FGF10–1 mM nicotinamide − 9 μM ROCK inhibitor − 0.5 μM TGF-β R Kinase Inhibitor IV -hydrocortison -forskolin -heregulinβ-1 | -advanced DMEM/F12 - 50 ng/ml human EGF − 250 ng/ml R-spondin1 − 100 ng/ml Noggin - 10 μMY27632 − 1 μM Jagged-1 - L-glutamine solution -penicillin/ Streptomycin and amphotericin B suspension | -Advanced DMEM/F12 1X - penicillin streptomycin 100 U·ml− 1 / 100 mg·ml− 1 - 10 mM HEPES - GlutaMax 100x 1X - Nicotinamide 1 mM - N2 supplement 1X - B27 supplement 1X - SB431542 0.5 μM - - R-Spondin 1, mouse 25% - EGF 10 ng·ml− 1 - Y-27632 9 μM | n.s. | - Advanced DMEM/F12 − 2 mM HEPES - 1 × GlutaMAX-I -1X B27 supplement − 10 nM Leu15-Gastrin I - 1 mM N-acetylcystein − 100 ng/mL recombinant human IGF-1 − 50 ng/mL recombinant human FGF-2 - 20% Afamin/Wnt3a CM - 1 μg/ mL humanR-spondin - 100 ng/mL Noggin − 500 nM A-83-01 − 200 U/mL penicillin/streptomycin − 10 μM Y-27632 | -DMEM/ F12 − 10% R-spondin1 - 2% B27 supplement - 10 mM HEPES − 1% Glutamax − 1.25 mM N-acetyl cysteine − 100 μg/mL Primocin - 1% Antibiotic- Antimycotic - 1 mM nicotinamide − 0.5 μM A 83–01 − 5 nM Neuregulin 1 - 5 ng/mL FGF-7 - 20 ng/mL FGF-10 − 100 ng/mL Noggin - 5 ng/mL EGF - 0.5 μM SB 202190 - 5 μM Y-27632 | - Y27632 10 μM -DMEM/F12 -L-glutamine 1X - Pen/Strep 1X - A83–01 0.5 μM -Nicotinamide 1 or 5 mM -N2 1X B27 minus vitamin A N-acetylcysteine 1X - 17-β Estradiol 1.25 mM - p38i 1 or 10 μM - EGF 50 ng/ml ± bFGF 2 ng/ml ± FGF10 10 ng/ml -Noggin (rec or CM) 10% or 100 ng/mL - RSPO1 (rec or CM) 25% or 50 ng/mL ±IGF1 20 ng/mL ±HGF 10 ng/mL ±NRG1 50 ng/mL | - ADF ± 25% conditioned human Wnt3A medium − 25% conditioned human RSPO1 medium − 12 mM HEPES − 1% GlutaMAX − 2% B27 − 1% N2 − 10 ng ml− 1 human EGF − 100 ng ml− 1 human noggin − 100 ng ml− 1 human FGF10 − 1 mM nicotinamide − 9 μM ROCK inhibitor − 0.5 μM TGF-β R Kinase Inhibitor IV -hydrocortison -forskolin -heregulinβ-1 |
Genomic characterization | WES (at passage 5) | WES | Not performed | WGS | 409-gene panel (on 3 out of 9 PDOs) | 121-gene panel | RNA-Seq analysis | 1053-gene panel (at median passage 4) | RNA-Seq analysis | WGS | WGS |
Concordance rate | 86% Allele-specific copy number, high concordance in ploidy and genomic burden | >  98% in somatic mutation, allelic imbalance and copy number variantions | n.s | High in in somatic mutation, allelic imbalance and copy number variations | High in somatic mutations | High in somatic mutations | Not performed | Median 59.1% of gene variants were shared; high concordance in copy number variations | n.s | High in in somatic mutation and copy number variations | 67% of single nucleotide variants, comparable copy-number states |
Drug screening | Not performed | Carboplatin Olaparib Prexasertib VE-822 | Seliciclib Milciclib PHA-793887 PHA-767491 BS-181 HCl BMS-265246 Flavopiridol HCl BMS-387032 AT7519 Dinaciclib Degrasyn R547 Alvocidib AZD5438 JNJ-7706621 THZ1 Palbociclib SNS-032 WZ3146 WZ8040 IMD0354 PD184352 AZD8330 Omipalisib BGT226 Quizartinib BGT226 Degrasyn Lapatinib Ditosylate Sorafenib Tosylate WZ8040 Lapatinib CHIR-124 CUDC-907 CUDC-101 NVP-AEW541 PHA-665752 GSK690693 | Paclitaxel Carboplatin Alpelisib Pictilisib MK2206 AZD8055 Niraparib Adavosertib Gemcitabine | Paclitaxel Cisplatin | Carboplatin | Cisplatin | Cisplatin Carboplatin Paclitaxel Docetaxel Vinorelbine Eribulin Topotecan SN-38 Etoposide Doxorubicin Gemcitabine Tamoxifen Trabectedin Olaparib Vorinostat Belinostat Cediranib Pazopanib Sunitinib Everolimus Trametinib Gefitinib Lapatinib | Carboplatin Taxol Mocetinostat Trametinib LY294002 AZD5363 BBI503 MK-1775 Sorafenib APR-246 CB5083 Napabucasin | Paclitaxel Cisplatin Doxorubicin Gemcitabine | Carboplatin Paclitaxel Gemcitabine Olaparib Niraparib Rucaparib Afatinib Vemurafenib Flavopiridol Adavosertib Alpelisib Adavosertib Afatinib AZD8055 Pictilisib Cobimetinib |