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