Zebrafish tumour xenograft models: a prognostic approach to epithelial ovarian cancerShow others and affiliations
2024 (English)In: npj Precision Oncology, E-ISSN 2397-768X, Vol. 8, no 1, article id 53Article in journal (Refereed) Published
Abstract [en]
Epithelial ovarian cancer (EOC) is the gynaecological malignancy with highest mortality. Although adjuvant treatment with carboplatin and paclitaxel leads to an objective response in similar to 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.
Place, publisher, year, edition, pages
NATURE PORTFOLIO , 2024. Vol. 8, no 1, article id 53
National Category
Urology and Nephrology
Identifiers
URN: urn:nbn:se:liu:diva-201678DOI: 10.1038/s41698-024-00550-9ISI: 001176665600001PubMedID: 38413842OAI: oai:DiVA.org:liu-201678DiVA, id: diva2:1845277
Note
Funding Agencies|VINNOVA (Swedish Governmental Agency for Innovation Systems) [2017-01444, H2020-MSCA-RISE-Crystal3, LIO-934261]; VINNOVA
2024-03-182024-03-182024-03-18