An in vivo avian paradigm to model human melanoma disease and perform fast and relevant preclinical studies

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. Innate resistance can involve transcriptional and epigenetic-based phenotypic adaptations, remaining yet unpredictable. 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-PDXTM). In this particular paradigm, we depict a fast and reproducible tumor intake of patient samples within the embryonic skin, preserving key molecular and phenotypical features. We provide the proof of concept that the AVI-PDXTM allows modeling melanoma patient diversity of responses to BRAFi/MEKi, in very short delays, hence positioning it as a valuable tool for the design of personalized medicine assays. GLO and GLO-R cells are a pair of BRAFV600-mutated melanoma cells derived from a metastatic patient, before (GLO) and after (GLO-R) emergence of resistance to vemurafenib + cobimetinib treatment