Mechanisms underlying hepatocellular carcinoma pathogenesis and impact of co-morbidities ageing of the immune system
HEP-CAR will transform the treatment of hepatocellular carcinoma (HCC) by increasing our understanding of common mechanisms underlying HCC development and will assess the impact of co-morbidities on disease pathogenesis and response to treatments. Specifically, we will:
HEP-CARpartners are world-leading experts in clinical, genetic, molecular, viral and immune driven aspects of hepatocellular carcinogenesis with expertise in writing and disseminating practical guidelines into the clinic. As a consortium, we have access to clinically well-characterised patient populations along with associated human biological material (HCC tissue, peripheral blood) and novel mouse models, allowing the integration of clinical and pre-clinical data sets. Thereby, HEP-CARis in a unique position to define the impact of co-morbidities and gender on HCC progression that will underpin future personalized strategies for prevention, diagnosis and development of new treatments for HCC. A wide-ranging genetic screen will identify cellular pathways deregulated in HCC and discriminate between those common to all and those specific for individual comorbidities.
Due to its asymptomatic nature early HCC detection is difficult, with many patients with advanced disease and poor prognosis. Current HCC surveillance includes serology and ultrasonography, but both tests have severe limitations for detecting early HCC. HEP-CARwill lay the foundation for new prognostic tests to diagnose early-stage HCC prior to its detection by ultrasonography: such screens have the potential to change current liver cancer management guidelines. As inflammation is one of the characteristic features of chronic liver disease and a major risk factor for developing HCC we will study the immune mechanisms contributing to progressive HCC1. We hypothesize that co-morbidities deregulate host immune responses and play a key role in HCC pathogenesis.
We will provide definitive answers to current uncertainties surrounding gender disparity and HCC, e.g. by elucidating the reasons why female European citizens are less likely to develop HCC compared to males.
We will combine our research and clinical excellence with the knowledge transfer and communication competence of leading organizations such as the European Association for the Study of the Liver (EASL) and the European Liver Patients Association (ELPA). Thus, HEP-CARwill generate tangible and sustained improvements in the understanding, prevention and management of HCC for all European citizens.