The search for biomarkers in systemic treatment of advanced hepatocellular carcinoma.
Recently, the amount of potential systemic treatment options for
patients with advanced hepatocellular carcinoma has increased
dramatically. While in 2016 only sorafenib was available, today more
than five drugs are approved by the FDA. However, the benefit of
each of these compounds in an individual patient is highly
unpredictable in the absence of guiding biomarkers. Therefore, the
development of predictive biomarkers is key to stratify treatment and
make substantial clinical progress. As there is a clear subgroup with
durable responses and prolonged survival on checkpoint inhibitors,
this project focuses on biomarker development in the field of
immunotherapy. Pre-treatment tissue biopsies of 25 patients will be
processed for single cell analysis (scRNA-seq and CITE-seq) to
elucidate the state of the immune microenvironment. Data will be
correlated with checkpoint inhibition response. From this, we will
derive potential clinically useful biomarkers which will be tested in an
independent cohort in the context of an international collaboration.
Moreover, in order to find signs of early response, serial liquid
biopsies of advanced HCC patients on any systemic therapy will be
analyzed. Dynamics in methylation levels of circulating DNA will be
assessed using an optimized capture bisulphite sequencing platform.
The overall aim of this project is to develop relevant biomarkers in
this setting that can proceed quickly to further validation steps and
ultimately clinical use.