PUBLICATION
Zebrafish Avatars: Toward Functional Precision Medicine in Low-Grade Serous Ovarian Cancer
- Authors
- Fieuws, C., Bek, J.W., Parton, B., De Neef, E., De Wever, O., Hoorne, M., Estrada, M.F., Van Dorpe, J., Denys, H., Van de Vijver, K., Claes, K.B.M.
- ID
- ZDB-PUB-240526-9
- Date
- 2024
- Source
- Cancers 16(10): (Journal)
- Registered Authors
- Keywords
- functional precision medicine, low-grade serous, ovarian cancer, zAvatars, zebrafish xenografts
- MeSH Terms
- none
- PubMed
- 38791891 Full text @ Cancers
Citation
Fieuws, C., Bek, J.W., Parton, B., De Neef, E., De Wever, O., Hoorne, M., Estrada, M.F., Van Dorpe, J., Denys, H., Van de Vijver, K., Claes, K.B.M. (2024) Zebrafish Avatars: Toward Functional Precision Medicine in Low-Grade Serous Ovarian Cancer. Cancers. 16(10):.
Abstract
Ovarian cancer (OC) is an umbrella term for cancerous malignancies affecting the ovaries, yet treatment options for all subtypes are predominantly derived from high-grade serous ovarian cancer, the largest subgroup. The concept of "functional precision medicine" involves gaining personalized insights on therapy choice, based on direct exposure of patient tissues to drugs. This especially holds promise for rare subtypes like low-grade serous ovarian cancer (LGSOC). This study aims to establish an in vivo model for LGSOC using zebrafish embryos, comparing treatment responses previously observed in mouse PDX models, cell lines and 3D tumor models. To address this goal, a well-characterized patient-derived LGSOC cell line with the KRAS mutation c.35 G>T (p.(Gly12Val)) was used. Fluorescently labeled tumor cells were injected into the perivitelline space of 2 days' post-fertilization zebrafish embryos. At 1 day post-injection, xenografts were assessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib and trametinib + luminespib. Subsequently, xenografts were euthanized and analyzed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n = 84) in vivo, with clear Ki67 staining, indicating proliferation. Zebrafish xenografts exhibited sensitivity to trametinib and luminespib, individually or combined, within a two-week period, establishing them as a rapid and complementary tool to existing in vitro and in vivo models for evaluating targeted therapies in LGSOC.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping