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- Title
Zebrafish tumour xenograft models: a prognostic approach to epithelial ovarian cancer.
- Authors
Lindahl, Gabriel; Fjellander, Sebastian; Selvaraj, Karthik; Vildeval, Malin; Ali, Zaheer; Almter, Rusul; Erkstam, Anna; Rodriguez, Gabriela Vazquez; Abrahamsson, Annelie; Kersley, Åsa Rydmark; Fahlgren, Anna; Kjølhede, Preben; Linder, Stig; Dabrosin, Charlotta; Jensen, Lasse
- Abstract
Epithelial ovarian cancer (EOC) is the gynaecological malignancy with highest mortality. Although adjuvant treatment with carboplatin and paclitaxel leads to an objective response in ~80% of these patients, a majority will relapse within two years. Better methods for assessing long-term treatment outcomes are needed. To address this, we established safe and efficacious doses of carboplatin and paclitaxel using IGROV-1 zebrafish-CDX models. Then fluorescently-labelled cell suspensions from 83 tumour biopsies collected at exploratory laparotomy of women with suspected EOC were generated and 37 (45%) were successfully implanted in zebrafish larvae. Among these 19 of 27 pathology-confirmed EOC samples (70%) engrafted. These zebrafish patient-derived tumour xenograft (ZTX) models were treated with carboplatin or paclitaxel and tumour growth/regression and metastatic dissemination were recorded. In a subgroup of nine patients, four ZTX models regressed during carboplatin treatment. All four corresponding patients had >24 months PFS. Furthermore, both ZTX models established from two patients having <24 months PFS failed to regress during carboplatin treatment. Seven of eight models seeding <6 metastatic cells were established from patients having >24 months PFS. In eleven of fourteen patients, FIGO stage I + II or III tumours gave rise to ZTX models seeding <4 or >4 metastatic cells, respectively. In conclusion, ZTX models predicted patients having >24 or <24 months PFS, based on response/no response to carboplatin. Furthermore, high metastatic dissemination in ZTX models correlated to shorter PFS and more advanced disease at diagnosis. These preliminary results suggest that ZTX models could become a useful prognostic tool in EOC treatment planning.
- Subjects
OVARIAN epithelial cancer; PROGNOSTIC models; BRACHYDANIO; CELL suspensions; DIAGNOSIS; TUMORS
- Publication
NPJ Precision Oncology, 2024, Vol 8, p1
- ISSN
2397-768X
- Publication type
Article
- DOI
10.1038/s41698-024-00550-9