An in vivo avian model of human melanoma to perform rapid and robust preclinical studies - Centre de recherche en cancérologie de Lyon (UMR INSERM 1052 ; CNRS 5286 ; Centre Léon Bérard) Accéder directement au contenu
Pré-Publication, Document De Travail Année : 2022

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

Résumé

Abstract Metastatic melanoma patients carrying a BRAF V600 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.

Dates et versions

hal-03854621 , version 1 (15-11-2022)

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Loraine Jarrosson, Stéphane Dalle, Clélia Costechareyre, Yaqi Tang, Maxime Grimont, et al.. An in vivo avian model of human melanoma to perform rapid and robust preclinical studies. 2022. ⟨hal-03854621⟩
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