Table 1 Key information and opinions in recent OC PDX research
From: Harnessing preclinical models for the interrogation of ovarian cancer
Patients’ material | Mice strain | Grafting site | Number of models | Grafting rate | Histology | Therapy | Genetical profiling | Original findings and opinions | Reference |
|---|---|---|---|---|---|---|---|---|---|
Tumor tissue | Nude | SQ | 61 | 46.92% | SOC, CCC, EMC, MOC, MMMT, Brenner | NI | YES | 1). engraftment rate of OC PDX was correlated with patients’ prognosis. 2). Differentially expressed genes selected according to PDX engraftment status could be a prognosis marker of CCC patients. | Shin, Ha-Yeon et al. [60] |
Tumor tissue | NOD/SCID, NRG, NSG | SQ | 33 | 76.74% | HGSOC | Cisplatin and/or paclitaxel | YES | 1). PDXs remained stable in histological and genetic features throughout propagation. 2). HGSOC PDX models faithfully recapitulated the chemotherapy response of corresponding patients. 3). Development of HGSOC PDX that can be visualized by bioluminescence imaging. | Cybula, Magdalena et al. [61] |
Tumor tissue | NPI | SQ | 92 | 58.23% | HGSOC, LGSOC, EMC, CCC, MOC | Paclitaxel + carboplatin/ cisplatin, carboplatin + doxorubicin | YES | 1). Despite certain deviations in transcriptomic level, OC PDXs retained the histology, protein expression, and genetic alteration of parental tumors 2). OC PDX showed significant similarity with patients in chemotherapy response. | Chen, Jiayu et al. [62] |
Tumor cell suspension | NOD/SCID, NSG | MFP | 38 | NI | HGSOC | Carboplatin | YES | 1). OC PDXs showed similar sensitivity to carboplatin as the patients’ tumor. 2). OC PDXs recapitulated the diversity of genomic alterations in HGSOC. 3). OC PDXs represented all HGSOC subtypes except for the immunoreactive group. | Cybulska, Paulina et al. [63] |
Ascites, pleural effusions | Nude, NSG | IP | 14 | 14.89% | HGSOC, ADENO, Mixed | Carboplatin and/or paclitaxel | YES | 1). Histologic and molecular features were preserved through PDX passaging and post-luciferization. 2). PDX models responded to first-line chemotherapy in a way reflective of the clinical features of OC. 3). Generation of PDX models with malignant ascites and pleural effusions may better reflect recurrent treatment-resistant OC. | Liu, Joyce F et al. [64] |
Tumor tissue | NSG | OTP | 37 | 92.50% | BRCAmut HGSOC | ATR/CHK1 inhibitor, PARP inhibitor | YES | 1). Establishment of HR-deficient HGSOC PDX models. 2). OC PDXs were suitable models for preclinical study of chemotherapies and targeted therapies based on RPPA identification | George, Erin et al. [65] |
Tumor tissue | Nude | SRC | 22 | 48.89% | SOC, CCC | Paclitaxel + carboplatin, EGFR inhibitor | YES | 1). Patients with successfully engrafted tumor had inferior OS. 2). Chemotherapy response of PDXs was concordant with that of patients. 3). Erlotinib significantly decreased the tumor weight of an CCC PDX in preclinical experiments. | Heo, Eun Jin et al. [66] |
Tumor tissue | NOD/SCID, NSG | SQ, OTP | 9 | NI | HGSOC | NI | YES | 1). OC PDXs maintained similar histologies, cellular compositions and oncogenic markers of original tumor. 2). Steroid hormone receptors loss and immunoresponsive genes alteration were obseved in PDX tumors. | Dong, Ruifen et al. [67] |
Tumor tissue, ascites | Nude | SQ, IP, OTP | 34 | 24.64% | SOC, EMC, CCC, MOC, Mixed, Brenner, others | Paclitaxel + cisplatin | YES | 1). OC PDXs were histologically similar to the corresponding patient tumor and comprised all the major ovarian cancer subtypes. 2). Othotopic transplantation resulted in peritoneal tumor dessemination and ascites. 3). Drug response of OC PDXs resembled corresponding patients. | Ricci, Francesca et al. [68] |
Tumor tissue | NOD/SCID | SQ, OTP | 10 | 83.33% | HGSOC | Cisplatin | YES | 1). HGSOC PDX models could inherit BRCA mutation and oncogene overexperssion in original tumor. 2). OC PDXs could be used for better design of future clinical trials. | Topp, Monique D et al. [69] |
Tumor cell suspension | NOD/SCID | IP | 168 | 74% | SOC, EMC, CCC, MOC, Mixed, Others | Carboplatin /paclitaxel | YES | 1). OC PDX retained key clinical and molecular features of primary tumor, demonstrating considerable diversity. 2). OC PDX biobank can serve as accurate surrogates for OC patients for individualized therapy development. | Weroha, S John et al. [70] |
Tumor tissue | NOD/SCID | SRC | 11 | 96% | SOC, MOC, GCT | NI | NO | 1). SRC xenografts and donor tissues showed highly similar histopathological features. 2). Subrenal capsule implantation yeilded achievable, consistently high enngraftment rate. | Lee, Cheng-Han et al. [71] |
Tumor tissue, ascites, pleural effusions | Nude | SQ, IP | 15 for IP 18 for SP | 28% for IP 30% for SP | SOC, ADENO, EMC, CCC, MMMT | NI | NO | 1). Overexpression of mutant P53 tended to influence the tumorigeneity of OC. 2). OC PDX panels are usful models for cancer biology and therapeutic studies. | Verschraegen, Claire F et al. [72] |
Ascites | Nude | SQ, IP | 4 | 20% | HGSOC | Cisplatin, adriamycin and cyclophosphamide | NO | 1). The histology of xenografts remained stable. 2). Genetic content in PDX was not markedly different from that of original tumor, with minimal variations through passages. 3). Heterogeneity of OC in chemotherapy response was reserved in xenografts. | Massazza, G et al. [73] |