Project description:131 patient-derived xenograft models were generated for non-small cell lung carcinoma and were profiled by analysis of gene copy number variation, whole exome sequence, methylome, transcriptome, proteome, and phospho(Tyr)-proteome. Proteome profiling resolved the known major histology subtypes and revealed 3 proteome subtypes (proteotypes) among adenocarcinoma and 2 in squamous cell carcinoma that were associated with distinct protein-phosphotyrosine signatures and patient survival. Proteomes of human tumor were discernible from murine stroma. Stromal proteomes were similar between histological subtypes, but two adenocarcinoma proteotypes had distinct stromal proteomes. Tumor and stromal proteotypes comprise signatures of targetable biological pathways suggesting that patient stratification by proteome profiling may be an actionable approach to precisely diagnose and treat cancer.
Project description:131 patient-derived xenograft models were generated for non-small cell lung carcinoma and were profiled at the genome, transcriptome and proteome level by analysis of gene copy number variation, whole exome sequencing, DNA methylation, transcriptome, proteome and phospho(Tyr)-proteome. At the proteome level, the human tumor and murine stroma were discernible. Tumor proteome profiling resolved the known major histological subtypes and revealed 3 proteome subtypes (proteotypes) among adenocarcinoma and 2 in squamous cell carcinoma that were associated with distinct protein-phosphotyrosine signatures and patient survival. Stromal proteomes were similar between histological subtypes, but two adenocarcinoma proteotypes had distinct stromal proteomes. Proteotypes comprise tumor and stromal signatures of targetable biological pathways suggesting that patient stratification by proteome profiling may be an actionable approach to precisely diagnose and treat cancer.
Project description:To characterize sotorasib resistance in lung adenocarcinomas (LUAD), we implanted pieces derived from a patient-derived KRAS-G12C positive xenograft (PDX) lung tumor model in immunocompromised mice
Project description:To address how intratumoral heterogeneity affects anti-cancer drug responses, we profiled transcriptomes of single cancer cells originating from lung adenocarcinoma patient-derived xenograft (PDX) tumors.
Project description:Lung cancer shows substantial genetic and phenotypic heterogeneity across individuals, driving a need for personalized medicine. Here we report lung cancer organoids and normal bronchial organoids established from patients tissues comprising five histological subtypes of lung cancer and non-neoplastic bronchial mucosa as in vitro models representing individual patient. The lung cancer organoids recapitulate the tissue architecture of the primary lung tumours and maintain the genomic alterations of the original tumours during long-term expansion in vitro. The normal bronchial organoids maintain cellular components of normal bronchial mucosa. Lung cancer organoids respond to drugs based on their genomic alterations: a BRCA2 mutant organoid to olaparib, an EGFR mutant organoid to erlotinib, and an EGFR mutant/MET amplified organoid to crizotinib. Considering the short length of time from organoid establishment to drug testing, our newly developed model may prove useful for predicting patient-specific drug responses through in vitro patient-specific drug trials.
Project description:Patient derived xenografts (PDXs) of human EGFR-mutant lung cancer were propagated in mice and treated with osimertinib or control to investigate the transcriptional adaption resposne.