Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Zebrafish avatars: towards functional precision medicine in low-grade serous ovarian cancer

Charlotte Fieuws
ORCID logo ,
Jan Willem Bek
,
Bram Parton
ORCID logo ,
Olivier De Wever
,
Milena Hoorne
,
Marta F Estrada
ORCID logo ,
Jo Van Dorpe
ORCID logo ,
Hannelore Denys
,
Koen Van de Vijver
ORCID logo ,
Kathleen B.M. Claes
* ORCID logo
Version 1 : Received: 20 March 2024 / Approved: 20 March 2024 / Online: 21 March 2024 (10:45:03 CET)

How to cite: Fieuws, C.; Bek, J.W.; Parton, B.; De Wever, O.; Hoorne, M.; Estrada, M.F.; Van Dorpe, J.; Denys, H.; Van de Vijver, K.; Claes, K.B. Zebrafish avatars: towards functional precision medicine in low-grade serous ovarian cancer. Preprints 2024, 2024031257. https://doi.org/10.20944/preprints202403.1257.v1 Fieuws, C.; Bek, J.W.; Parton, B.; De Wever, O.; Hoorne, M.; Estrada, M.F.; Van Dorpe, J.; Denys, H.; Van de Vijver, K.; Claes, K.B. Zebrafish avatars: towards functional precision medicine in low-grade serous ovarian cancer. Preprints 2024, 2024031257. https://doi.org/10.20944/preprints202403.1257.v1

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 labelled tumor cells were injected into the perivitelline space of 2 days post fertilization zebrafish embryos. At 1 day post-injection xenografts were as-sessed for tumor size, followed by random allocation into treatment groups with trametinib, luminespib, and trametinib + luminespib. Subsequently xenografts were euthanized and analysed for apoptosis and proliferation by confocal microscopy. Tumor cells formed compact tumor masses (n=84) in vivo and 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.

Keywords

ovarian cancers; zebrafish xenografts; functional precision medicine; zAvatars; low-grade serous

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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