Hepatology: Liquid Biopsy and Carcinogenesis

Liver cancer is a major global health problem, with more than 850,000 new cases annually, whose incidence is increasing in association with the obesity pandemic. It is the sixth most frequent neoplasm and the third leading cause of cancer-related death, mostly due to late diagnosis and limited efficacy of available treatments.

Our group, integrated in the Cancer Center Clínica Universidad de Navarra, has been investigating for more than 25 years the molecular mechanisms involved in the process of hepatocarcinogenesis to identify new therapeutic targets and diagnostic biomarkers. We have proven experience in the development of animal models, isolation of primary liver cells and generation of organoids.

We have identified the dual role of molecules such as amphiregulin growth factor, which is induced in the liver to protect it against damage, but participates in its malignant transformation. We have also demonstrated the important role that dedifferentiation or loss of hepatocyte identity plays in the process of hepatocarcinogenesis, and the relevance of transcription factors such as HNF4a or splicing factors such as SLU7, whose multiple functions we are still unraveling. 

In our quest to develop non-invasive liquid biopsy methods to improve the management of patients with liver tumors, we have developed a method based on the detection of mutations by massive sequencing in bile to identify the presence of cholangiocarcinomas or pancreatic tumors. Likewise, based on our experience in the field of epigenetics, specifically DNA methylation, we are developing liquid biopsy strategies for the early diagnosis of hepatocarcinoma.