Table 2 Key information and opinions in recent OC PDO research

Tumor tissue

13

85%

Matrigel

≥ 3 passages

HGSOC, EMC, CCC, SBT, KruKenberg

PARP inhibitors

YES

1). OC PDOs’ response to first-line chemotherapy correlated with clinical response.

2). PDOs resembled parental tumors with an average overlap of 91.5% of SNVs and SVs.

3). PDO model is capable of evaluating PARPi sensitivity, exploring resistant mechanisms, and identifying effective combination strategies.

Tao, Mengyu et al. [116]

Human iPSC

3

NI

Matrigel

NI

STIC

PARP inhibitors

YES

1). BRCA1^mut patient iPSC lines can differentiate into FTE.

2). BRCA1^mut fallopian tubes recapitulate OC tumorigenesis in vitro/vivo.

3). BRCA1^mut fallopian tubes provided model to predict disease severity.

4). BRCA1^mut fallopian tube organoids provided platform to study drug efficacy.

Yucer, Nur et al. [117]

Tumor tissue, Ascites

21

82.7%^a

Matrigel

≥ 2 passages

HGSOC, LGSOC, CCC, EMC

Trastuzumab, gemcitabine, bevacizumab, topptecan, paclitaxel, carboplatin

NO

1). The establishment of gynecological cancer PDOs was feasible and helpful to studying the impact of drugs in a clinically meaningful time window.

2). Neoadjuvant therapy negatively affected the success rate of PDO generation.

Bi, Jianling et al. [118]

Tumor tissue

25

80%

Matrigel

2 ~ 5 passages

HGSOC, EMC, CCC, MOC, MBT, others

23 FDA-approved drugs

YES

1). Organoids captured subtype-specific characteristics of OC and replicated the mutational profile of the primary tumors.

2). Using PDO was a reliable strategy for drug testing.

Nanki, Yoshiko et al. [119]

Tumor tissue, Ascites

36

NI

Matrigel

NI

HGSOC, LGSOC, EMC, CCC, S/MBT, MOC

16 chemo- and targeted therapies

YES

1). OC PDOs could serve as drug screening models in OC research.

2). OC PDOs recapitulated patients’ responses to carboplatin and paclitaxel.

3). OC PDOs displayed inter- and intrapatient drug response heterogeneity.

4). OC PDO drug response heterogeneity can be partially explained by genetic aberrations.

de Witte, Chris Jenske et al. [120]

Ascites, pleural effusions

14

NI

Cultrex BME

Short-term for ≥6 days

HGSOC

12 chemo- and targeted therapies

YES

1). A short-term PDO culture can be applied to study drug susceptibilities for individual patient.

2). Drug screen on PDO could be beneficial for treatment-exhausted subgroup.

Chen, Hui et al. [121]

Tumor tissue

12

44%

Cultrex BME

1 ~ 2 passages

HGSOC, LGSOC, CCC, MOC

Paclitaxel, cisplatin, doxorubicin, gemcitabine

YES

1). Established organoids demonstrated parental tumor-dependent morphology and biology, retained parental tumor’s marker expression and mutational landscape.

2). Organoids exhibited tumor-specific sensitivity to clinical chemotherapies.

Maenhoudt, Nina et al. [122]

Tumor tissue

15

30%

Matrigel

6 ~ 26 passages

HGSOC

Carboplatin

YES

1). OC PDOs matched the mutational and phenotypic profiles of original tumor.

2). Wnt pathway activation led to growth inhibition of OC PDOs and active BMP signaling is almost always required for the generation of HGSOC organoids.

Hoffmann, Karen et al. [123]

Tumor tissue

9

60%

Matrigel

NI

EMC, Brenner, HGSOC, MOC, SBT

Paclitaxel, cisplatin

YES

1). PDOs retained both histological and molecular features and intra-tumoral heterogeneity of parental tumors.

2). Organoids facilitated the preclinical studies on both inter- and intra-tumor heterogeneity.

Maru, Yoshiaki et al. [124]

Tumor tissue

56

65%

Matrigel

3 ~ 31 passages

HGSOC, LGSOC, EMC, CCC, MOC, S/MBT

Paclitaxel, carboplatin, alpelisib, pictilisib, MK2206, AZD8055, niraparib, adavosertib, gemcitabine

YES

1). OC organoids recapitulate histological and molecular features of the original lesions, recapitulating intra- and interpatient heterogeneity, and can be genetically manipulated.

2). OC organoids can be used for drug-screening and capture subtype-specific responses to chemotherapy, including the development of chemoresistance in recurrent OC.

3). OC organoids can be engrafted to form corresponding PDX, enabling in vivo drug-sensitivity tests.

Kopper, Oded et al. [115]

Tumor tissue, pleural effusions

33

80–90%

Matrigel

2 passages

HGSOC, LGSOC

Carboplatin, olaparib, prexasertib, VE-822

YES

1). OC PDOs matched the parental tumors, both genetically and functionally.

2). PDOs can be used for DNA repair profiling and therapeutic sensitivity testing and provide a rapid means of evaluating targetable defects in the parent tumor, facilitating better therapeutic options.

Hill, Sarah J et al. [114]