Targeting p53 in liver disease associated with metabolic syndrome

Liver cancer (HCC) is a lethal malignancy with few treatment options, poor prognosis, and rising rates of prevalence.
HCC arising from non-alcoholic steatohepatitis (NASH) represents an increasing fraction of HCC mortality, and
treatment options for advanced NASH are similarly scarce. Current prevention techniques of weight-loss, diet, and
exercise are insufficient to stem burgeoning rates of liver disease associated with metabolic syndrome (MetS-LD)
which presage significant growth in patients harbouring advanced MetS-LD (NASH) and HCC. This problem is especially
acute in Scotland, where rates of MetS and HCC are already the highest in the UK, and where the problem is further
compounded by the generally poorer health and higher rates of additional co-morbidities (the ‘Glasgow Effect’) in
Scotland. To avert a potential crisis of HCC, there is an urgent need to increase our understanding of the factors
directing MetS-LD progression to HCC. Insights into the pathways that shape MetS-LD can then be used to develop
new biomarkers to monitor the risk of disease progression in human MetS-LD patients. Detailed understanding may
also reveal new interventions to intercept tumourigenesis in MetS-LD.
This proposal builds on significant preliminary data to test the hypothesis th