Project description
Improving outcome of patients with advanced liver disease
The ERC-funded FIBCAN project will research innovative solutions for fibrosis and liver cancer, which is one of the deadliest in the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and almost always results in advanced liver fibrosis. In this context, FIBCAN will identify urgently needed targets for prevention and treatment of fibrosis-driven liver cancer. Specifically, it will investigate Claudin-1 as a target for prevention and treatment of fibrosis-driven HCC. Studies show a connection between Claudin-1 and liver fibrosis and hepatocarcinogenesis as well as overall and liver-specific patient death. The project expects to deliver novel therapeutic strategies for further clinical development.
Objective
Advanced liver diseases such as cirrhosis and hepatocellular carcinoma (HCC) are major challenges for global health. HCC is the second leading and fastest rising cause of cancer death worldwide. Viral and metabolic liver disease are the main risk factors for HCC, which nearly always arises in advanced liver fibrosis. For metabolic liver disease approved therapies are absent. Cure or suppression of viral infection cannot eliminate the HCC risk in patients with advanced fibrosis. Despite significant progress, therapeutic options for established HCC are still limited in efficacy and safety. Importantly, patient survival in HCC is dependent on the underlying fibrotic liver disease which is not targeted by approved HCC therapies. Addressing these unmet medical needs, FIBCAN aims to identify urgently needed targets for prevention and treatment of fibrosis-driven liver cancer. A key focus of FIBCAN will be the investigation of Claudin-1 as a previously undiscovered target for prevention and treatment of fibrosis-driven HCC. Our own data obtained in patient-derived model systems and tissues provide solid evidence that Claudin-1 is implicated in liver fibrosis and hepatocarcinogenesis, and overall and liver-specific patient death. To discover novel targets, we will apply a liver disease discovery platform modeling the clinical cell circuits of cirrhotic patients progressing to HCC combined with single cell RNA-seq and spatial transcriptomics of patient tissues. Proof-of-concept studies of target-specific compounds combined with biomarker discovery in cutting-edge patient-derived model systems will deliver novel strategies for further clinical development. A strong collaboration with pharma will lead to rapid translation of the FIBCAN program into the clinic. By delivering urgently needed therapeutic strategies for advanced liver disease and HCC, this proposal will have a marked impact on the management and outcome of patients with advanced liver disease in Europe and beyond.
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
75654 Paris
France