Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.

For example, in 3 cases involving pre-treatment, on-treatment (recurrence), and post-treatment (acquired resistance) samples, we found that 317 genes showed a trend of increased expression in at least two samples and that 389 genes showed decreased expression in at least two samples (Fig. 6a and Supplementary Fig. 9a–d ).

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For the WES data, analyses of single-nucleotide variants (SNVs) and of copy number variants (CNVs) indicated that increased drug resistance is often accompanied by an increasing trend for mutations in candidate cancer genes in the Network of Cancer Genes 24 , such as ERBB2 , IL24 , E2F1 , CDK1, MMP10, MMP13, etc.

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