Squamous cell carcinomas (SCCs), which arise at a variety of anatomical sites from stratified squamous epithelium, represent the most frequent human solid malignancies and are a major cause of cancer mortality. Genomic landscaping studies have identified a ’classic subtype’ of SCC, including lung, head and neck and oesophageal SCCs, that is characterised by frequent NRF2 and KEAP1 mutations. We aim to use functional investigations of the NRF2 pathway and integrated proteogenomic analyses to further characterise this classic subtype in SCCs across multiple anatomical sites. This proposal will investigate its molecular pathogenesis and provide new precision medicine strategies for diagnosis, prevention and treatment including novel NRF2 inhibitors as part of a unified investigational approach to the biology, clinical investigation and treatment of SCCs.
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