An in vivo avian model of human melanoma to perform rapid and robust preclinical studies

Jarrosson, L.; Dalle, S.; Costechareyre, C.; Tang, Y.; Grimont, M.; Plaschka, M.; Lacourrege, M.; Teinturier, R.; Le Bouar, M.; Maucort-Boulch, D.; Eberhardt, A.; Castellani, V.; Caramel, J.; Delloye-Bourgeois, C.

doi:10.1101/2022.10.12.511927

bioRxiv · 10.1101/2022.10.12.511927

An in vivo avian model of human melanoma to perform rapid and robust preclinical studies

Jarrosson, L.·Dalle, S.·Costechareyre, C.·Tang, Y.·Grimont, M.·Plaschka, M.·Lacourrege, M.·Teinturier, R.·Le Bouar, M.·Maucort-Boulch, D.·Eberhardt, A.·Castellani, V.·Caramel, J.·Delloye-Bourgeois, C.

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Abstract

Metastatic melanoma patients carrying a BRAFV600 mutation can be treated with BRAF inhibitors (BRAFi), in combination with MEK inhibitors (MEKi), but innate and acquired resistance invariably occurs. Resistance can involve transcriptional- and epigenetic-based phenotypic adaptations, as yet unpredictable. Predicting patient response to targeted therapies is crucial to guide clinical decision. We describe here the development of a highly efficient patient-derived xenograft model adapted to patient melanoma biopsies, using the avian embryo as a host (AVI-PDX). In this in vivo paradigm, we depict a fast and reproducible tumor engraftment of patient samples within the embryonic skin, preserving key molecular and phenotypic features. We show that sensitivity and resistance to BRAFi/MEKi targeted therapies can be reliably modeled in these AVI-PDX, as well as synergies with other drugs, such as HDACi. We further provide proof-of-concept that the AVI-PDX models the diversity of responses of melanoma patients to BRAFi/MEKi, within days, hence positioning it as a valuable tool for the design of personalized medicine assays and for the evaluation of novel combination strategies.

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Jarrosson, L., Dalle, S., Costechareyre, C., Tang, Y., Grimont, M., Plaschka, M., Lacourrege, M., Teinturier, R., Le Bouar, M., Maucort-Boulch, D., Eberhardt, A., Castellani, V., Caramel, J., Delloye-Bourgeois, C.. 2022-10-13. An in vivo avian model of human melanoma to perform rapid and robust preclinical studies. https://doi.org/10.1101/2022.10.12.511927

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