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Fig. 5 | BMC Cancer

Fig. 5

From: The design, analysis and application of mouse clinical trials in oncology drug development

Fig. 5

Biomarker discovery and MoA study in MCTs. (a-b): A MCT of 27 gastric cancer PDXs treated with cetuximab. EGFR is ranked 157th among all genes based on Spearman rank correlation between EGFR expression and TGI (a), but is the top gene in predicting cetuximab efficacy based on a linear mixed model (LMM) (b). (c-e): A MCT of 16 PDXs treated with intraperitoneal injection of Irinotecan (100 mg/kg, once per week for 2 to 3 weeks). (c): R-HAS-160170, the cell cycle pathway in Reactome2016 database, is consistently ranked as the most enriched pathway with 100 to 2000 top genes selected by a LMM, superior to top genes selected by methods based on categorical endpoints (e.g., RECIST, Table S2) and continuous endpoints (e.g., TGI). (d): DNA replication initiation (GO: 0006270) is the most enriched GO term based on top genes selected by the LMM. (e): A highly enriched protein-protein interaction network (p-value< 10− 16) consisted of 23 genes in the top 100 genes selected by the LMM. Red-colored nodes are ones involved in cell cycle (GO: 0007049). Dashed horizontal lines in (c-d) denotes p-value = 0.01. (f): Mean tumor growth curves for PDXs with highest and lowest ERCC1 mRNA expression in a MCT of 21 gastric PDXs treated by cisplatin

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