Table 2.
Key information and opinions in recent OC PDO research
| Patients’ material | Number of models | Success rate | Extracellular matrix | Expansion | Histology | Therapy | Genetical profiling | Original findings and opinions | Reference |
|---|---|---|---|---|---|---|---|---|---|
| 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). BRCA1mut patient iPSC lines can differentiate into FTE. 2). BRCA1mut fallopian tubes recapitulate OC tumorigenesis in vitro/vivo. 3). BRCA1mut fallopian tubes provided model to predict disease severity. 4). BRCA1mut 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] |
iPSCs Induced pluripotent stem cells, HGSOC High-grade serous ovarian carcinoma, EMC Endometrioid carcinoma, CCC Clear cell carcinoma, SBT Serous borderline tumor, STIC Serous tubal intraepithelial carcinoma, LGSOC Low-grade serous ovarian carcinoma, MOC Mucinous carcinoma, MBT Mucinous borderline tumor, PARP Poly ADP-ribose polymerase, PARPi PARP inhibitors, FDA Food and drug administration (USA), SNV Single nucleotide variant, SV Structural variant, NI Not informed
aoverall success rate for OC and endometrial tumor organoids