Transgenic Drosophila As A Drug-Screening Platform In Colorectal Cancer And Medullary Thyroid Cancer.

e23164Background: Solid tumors are typically driven by genetic changes in multiple signaling pathways. While drugging single “actionable” targets can be effective, this approach fails to address tumor complexity or whole body toxicity and often fails to provide durable response. Methods: We screen subjects with metastatic colorectal (CRC), medullary thyroid (MTC) cancers and an exploratory cohort. Available tumor tissue and a non-tumor control from the same patient are assayed by whole exome sequencing (WES), a targeted panel to guarantee sensitivity in known oncogenic hotspot regions, and a SNP microarray. Somatic tumor-specific mutations and rare germline variants are analyzed with a set of bioinformatics tools to predict their functional impact, and copy number analysis is carried out to identify amplifications or deletions. Variants predicted to be deleterious are considered for inclusion in the final avatar along with known oncogenic drivers. Candidate genes are validated by additional assays; 10-12 ...