Enabling Precision Medicine through Oesophageal Cancer Proteogenomics

Capitalising on technological advances in next generation sequencing, genomic landscaping projects have provided a comprehensive catalogue of genetic abnormalities in human cancer, and in some tumour types provided classifications useful for clinical decision making. However the clinical impact of this work is limited by inadequate understanding of how variations in cancer genomes cause changes to the cellular proteome and how this affects the cancer cell phenotype and ultimately the clinical phenotype. In collaboration with the Scottish genomes partnership, we have combined whole genome sequencing and mass spectrometry based quantitative proteomics to perform an integrated proteogenomic analysis of oesophageal adenocarcinoma. This approach has provided functional insights that had not been possible with genomic studies alone, and in doing so suggested key disease drivers and pathogenic mechanisms .In this project, disease mechanisms will be functionally validated using in vitro models with priority given to those with the highest potential translational impact as targets e.g. repurposing of existing targets and agents to application in oesophageal cancer precision medicine strategies, or new first in class therapies.