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Epigenetics, microenvironment and liver cancer

Epigenetics, microenvironment and liver cancer (M. Levrero/M. Zeisel)

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, is a major cause of liver transplantation and cancer death worldwide. The vast majority of HCC can be associated with a well-characterized underlying risk factor, including chronic infection with hepatitis B, D and C viruses (HBV, HDV, HCV), excessive alcohol consumption and metabolic disorders (metabolic dysfunction-associated steatohepatitis (MASH)). Although the risk of developing HCC can be reduced in patients by treatment of the underlying cause (e.g. by HCV clearance, suppression of HBV replication, or alcohol abstention), effective strategies to prevent cancer development in patients with advanced fibrosis and established cirrhosis are still lacking. Patients with advanced HCC carry a very poor prognosis and despite recent improvements, treatment options remain largely unsatisfactory.

Driving forces in hepatocyte transformation, HCC development and progression include chronic inflammation, DNA damage and epigenetic modifications. All etiologic factors seem to act through similar mechanisms that converge to affect common pathways. During the past years, the team’s research efforts have enabled to gain new knowledge on i) the epigenetic changes that precede and accompany HCC development and progression; ii) the interaction of HBV, HDV and HCV with the host epigenome; iii) the molecular and immunological basis of viral pathogenicity and persistence in the setting of HBV and HDV chronic liver diseases.

Projects

Current research axes aiming at the characterization of the epigenetic changes in virus- and non-virus-related HCC focus on

1) histone methyltransferases as HCC epi-drivers and therapeutic targets

2) HBV and HDV proteins as epigenetic modulators in viral pathogenicity and HCC development

Furthermore, the team’s translational research axes include the design of a diagnostic test to assess curative treatments for hepatitis B as well as novel strategies to improve liver grafts prior to transplantation. The team is also part of a EU-funded collaborative network to evaluate novel immunomodulatory strategies for HBV cure.

These research efforts profit of a vast network of national and international collaborations with access to large cohorts of HBV/HDV, HCV and HCC patients and of the direct participation of EpiLiCan members to the strong clinical research program at the Hôpital de la Croix Rousse.

  • Contact

    Massimo Levrero
    Bâtiment Inserm
    151 Cours Albert Thomas
    69424 Lyon Cedex 03

    massimo.levrero@inserm.fr

    04 72 68 19 79

    04 72 68 19 70 (secretariat)

     

    Mirjam Zeisel
    Bâtiment Inserm
    151 Cours Albert Thomas
    69424 Lyon Cedex 03

    mirjam.zeisel@inserm.fr

    04 72 68 19 58

    04 72 68 19 70 (secretariat)

  • Team members
  • Publications
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Team members

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Publications