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Table 1 Key details and findings of studies on OC PDOs

From: Patient-derived organoids and high grade serous ovarian cancer: from disease modeling to personalized medicine

  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
  1. S Serous
  2. HGS high grade serous
  3. LGS Low grade serous
  4. HGM High grade mixed type
  5. HGP High grade peritoneal
  6. CS carcinosarcoma
  7. E endometrioid
  8. CC Clear cell
  9. SBT Serous borderline tumor
  10. M mucinous
  11. MBT Mucinous borderline tumor
  12. BBT Borderline Brenner tumor
  13. MBT Malignant brenner tumor
  14. MCB Mucinous Cystoadenoma borderline
  15. MMMT Malignant mixed mesonephric tumor
  16. NACT neoadjuvant chemotherapy
  17. n.s. not specified
  18. * the study contains data from other cancer types
  19. ** dysgerminoma, thecoma, serous cystadenofibroma, carcinosarcoma, and fibroma
  20. *** only referred to successfull organoids