Project Details
Projekt
Defining the molecular landscape of NASH-related HCC
Applicant
Dr. Christopher Schrecker
Subject Area
Gastroenterology
Term
from 2019 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 428434284
Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of end-stage liver disease and hepatocellular carcinoma (HCC) worldwide. The obesity pandemic has led to a surge in NAFLD and its more advanced form, non-alcoholic steatohepatitis (NASH), and is predicted to cause a dramatic rise in liver cancer incidence. NASH-HCC frequently occurs in non-cirrhotic livers, and tumours tend to be larger at diagnosis and less amenable to curative therapies, compared with HCC of other aetiologies. Our understanding of the molecular landscape of HCC arising from viral or alcoholic liver disease has increased significantly in recent years, but a comprehensive classification of NASH-HCC is still lacking. We now aim to comprehensively characterise the molecular aberrations that drive NASH-mediated tumorigenesis. Tissue specimens and blood samples from patients with NASH and NASH-HCC will be profiled by whole exome sequencing and RNA-seq. We will first characterise the genetic landscape of NASH-HCC tumours, to unveil unique oncogenic driver mutations and aberrantly activated pathways. We believe that the key drivers of disease progression differ from those found in HCC of other aetiologies. Next, we will dissect the oncogenic and immune-related pathways that characterise the premalignant field defect predisposing to liver cancer in patients with NASH. We will then devise a liquid biopsy approach to ameliorate the diagnostic accuracy of liver cancer screening in patients with NASH, and identify actionable targets in patients with advanced NASH-HCC. Ultimately, our findings will lead to targeted therapies for NASH-related HCC, one of the deadliest consequences of the obesity pandemic.
DFG Programme
Research Fellowships
International Connection
USA
