An avian embryo patient-derived xenograft model for preclinical studies of human breast cancers.

Lack of preclinical patient-derived xenograft (PDX) cancer models in which to conduct large scale molecular studies seriously impairs the development of effective personalized therapies. We report here on an in vivo concept consisting of implanting human tumor cells in targeted tissues of an avian embryo, delivering therapeutics, evaluating their efficacy by measuring tumors using light sheet confocal microscopy, and conducting large scale RNAseq analysis to characterize therapeutic-induced changes in gene expression. The model was established to recapitulate triple negative breast cancer (TNBC) and validated using TNBC standards of care (SOCs) and an investigational therapeutic agent. Overall design: Triple negative breast cancer cells (the MDA-MB-436 cell line) were transplanted into chicken embryos (AVI-cellDX). Two treatments were injected intravenously: 1-excipient (= control = 0.9% NaCl); 2-a mix of gemcitabine and carboplatin. We then performed whole RNASeq analyses. For each condition, the number of significantly upregulated and downregulated transcripts as compared to control medium were homogeneously distributed. Each condition is in duplicates.