Project 3 has the objective to characterize and subtype biliary tract cancer in a human pluripotent stem cell-based organoid model.
Although rare, biliary tract cancer (BTC) is associated with high mortality. Moreover, BTC displays significant heterogeneity in terms of location: intra- or extrahepatic, as well as in the oncogenic mutations – all not ideally addressed by current standard treatments.
Indeed, we hypothesize that the mutation signature impacts the development of tumor subtypes, and their therapeutic features.
To answer this, P3 aims to build and characterize a biliary organoid model comprising various known BTC mutations. Following biliary differentiation, doctoral researchers will analyze organoid growth, morphology, and gene expression by RNA-seq. Then, the PhD will determine the effect on tumor development in an ex vivo long-term culture, for example by immunohistochemical phenotyping as well as whole exome sequencing and finally, validate this in patient biomaterials from known tumor subgroups.
The overall goal is a biliary tumor model that allows to determine the impact of specific genetic insults on tumor subtype development, heterogeneity and therapy.