Translating genomic alterations into novel therapeutic targets in head and neck cancer through computational and functional approaches

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 DESCRIPTION (provided by applicant): Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease with few molecularly-based therapeutics. Recent genomic studies of HNSCC have identified numerous genomic alterations, but the alterations are dominated by tumor suppressor genes and untargetable oncogenes. Nevertheless, we hypothesize that novel molecular therapeutic targets are present in HNSCC and that these targets exist in parts of the data that have not been effectively analyzed. We propose to combine existing genomic data with computational approaches and in vivo pathway analysis to identify novel candidate targets in HNSCC. These candidate targets will be functionally tested in a high-throughput in vivo screening system in HNSCC lines with known genotype. Validated targets will be tested for genotype co-dependencies, and any known drug targets will be tested in preclinical xenograft models. Targets that are not currently druggable will have their pathways computationally and experimentally analyzed for additional targets that will be functionally tested. All experiments wil be performed in vivo in genomically characterized models. We aim to generate an extensive list of functionally validated novel targets for HNSCC that will be candidates for drug development pipelines.