In vivo modeling of tumor heterogeneity in hepatocellular carcinoma

Résumé :

Our research aims at a better understanding of how various combinations of oncogenic events drive tumorigenesis. We address two major questions in cancer biology, within the context of inter-tumoral heterogeneity: (1) what mechanisms underlie oncogenic cooperation in shaping of the tumor cell fate, and (2), how does the genetic identity of a tumor influence its interactions with the microenvironment ?

We explore these questions in the context of hepatocellular carcinoma (HCC), the most common primary liver cancer. Our approach combines functional studies with advanced preclinical mouse models, particularly in vivo hepatocyte transfection via hydrodynamic gene transfer. We focus our investigations on tumors driven by either FGF19 overexpression or a spectrum of p53 mutations.

In this talk at IAB, I will present recent findings on these two distinct families of hepatic tumors. Our ultimate goal is to elucidate how the genetic profile of HCC shapes the tumor cell phenotype, its interactions with the tumor microenvironment—especially immune cells—and its response to treatments.

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Contact : thomas.decaens@univ-grenoble-alpes.fr