PDAC Biomarker Identification And Validation

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PDAC biomarker identification and validation. Biomarkers in ex vivo expanded CTCs will be recognized by stringent statistical analysis and subjected to further characterization in three studies. First, we will confirm the association of biomarkers with CTCs and CTC-PDX models. Second, the biomarkers will be validated for correlation with clinical PDAC metastasis and therapeutic resistance. Finally, we will retrospectively test the application of selected biomarkers in PDAC diagnosis, treatment evaluation and disease prognosis. As biomarkers could be in the form of genomic abnormalities or transcriptional aberrations, corresponding methods will be used for validation, which we have previously reported (118-120). The ultimate objective is to …show more content…
The aCGH assay will be an essential tool to assess the genomic changes. Based on the results of SKY and aCGH analyses, representative CTC cultures will be subjected to mutation screening in CTC, CTD-PDX and biopsy materials by whole genome sequencing using NGS for comprehensive molecular profiling of abnormalities at the nucleotide level. NGS data will be transferred to Palanisamy, who will carry out biostatistics and bioinformatics analysis. Given the unbiased nature of NGS analysis, we anticipate identifying new druggable genomic mutations on a personalized …show more content…
The function of many coding gene is known and protein products from “driver” gene fusion can often be exploited as therapeutic targets (2). Our prior research on druggable gene fusions with RAF kinase (Figure 5) provides an example to explore expressional profiling and NGS data for identifying new “druggable” gene fusions and other actionable molecular markers. Given the unprecedented prevalence of gene rearrangements in PDAC, we expect additional “druggable targets” to occur in our study population. Based on the sequencing data, we will validate gene fusions by RT-PCR at the RNA level followed with FISH to confirm gene rearrangement. Recurrent fusions will be evaluated for oncogenic activity using expression constructs in normal pancreatic epithelial cells. At the end of the

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