Peritoneal metastasis of colorectal cancer (pmCRC): identification of predictive molecular signatures by a novel preclinical platform of matching pmCRC PDX/PD3D models

According to tumor heterogeneity, enrichment or loss of individual tumor cell types during model generation, some occurring cancer-related mutations were not detected in every sample of the respective model. In turn, analyzing the transcriptomes of patient metastases and derived models according to cancer hallmark gene signatures (including DNA repair in general), showed similar patterns of gene set enrichments at transcriptome and proteome level (Fig. Furthermore, gene set enrichment analysis (GSEA) of combined PDX models showing treatment response to 5-FU versus resistant models resulted in significantly enriched gene sets indicating DNA repair (ES = 0.44, p = 0.009), specifically NER (ES = 0.42, p = 0.002), and response to veliparib (ES = 0.62, p