Hepatology: Carcinogenesis (HEPACAN)

"Knowing the molecular mechanisms involved in the development of liver cancer has allowed us to identify new therapeutic targets and develop non-invasive early diagnosis strategies."

DR. CARMEN BERASAIN LASARTE
RESEARCHER. HEPATOLOGY RESEARCH GROUP: CARCINOGENESIS (HEPACAN)

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 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.

Dra. Carmen Berasain

GROUP LEADER

+34 948 194 700 | Ext. 81 4020
cberasain@unav.es
Research profile

Objectives of the Hepatology: Carcinogenesis (HEPACAN)
Research Group

Our goal is to deepen our understanding of the molecular mechanisms involved in the development of liver cancer in order to identify therapeutic targets and diagnostic markers. Our more specific current objectives are:

To deepen in the molecular mechanisms of hepatocarcinogenesis, with special emphasis on hepatic dedifferentiation and alterations in gene expression.

To develop therapeutic strategies for hepatocarcinoma against targets identified by the group.

Early detection of liver cancer using liquid biopsy strategies.

LIVER CANCER

Improve diagnosis and prognosis

Our ultimate interest is to improve the diagnosis and prognosis of patients with liver cancer by investigating the molecular mechanisms involved using plasma, bile and liver samples from patients, cell lines and animal models.

Lines of research

PI: Carmen Berasain

Co-IP: Maria Arechederra

Objectives:

  • To delve into the dedifferentiation mechanisms associated with the process of hepatocarcinogenesis.
  • To identify epigenetic, transcriptional and splicing alterations in hepatocarcinogenesis.  
  • Characterize the molecular mechanisms regulated by SLU7 (SLUTOME).
  • To evaluate SLU7 as a therapeutic target for hepatocarcinoma (APTASLU).

PI: Maria Arechederra.

Co-PI: Carmen Berasain

Objectives:

  • To develop liquid biopsy strategies in bile for the management of patients with malignant biliary strictures (BILEMUT).
  • To develop plasma liquid biopsy strategies for the management of patients with HCC (HEPAMETH).

Hepatocyte dedifferentiation

We have contributed to demonstrate the important role that hepatocyte dedifferentiation plays during loss of function and malignant transformation of the liver in chronic disease.

In this context we have identified important players such as amphiregulin and SLU7, establishing links between inflammation, endogenous liver protective response, metabolic dysfunction and genomic instability. 

We have recently demonstrated the great potential of analyzing DNA mutations present in bile collected during endoscopic retrograde cholangiopancreatography (ERCP) in patients with biliary stricture to sensitively and early diagnose the presence of cholangiocarcinoma and pancreatic cancer.

Furthermore...

Drs. Carmen Berasain and María Arechederra are founders of the BILEBANK project financed in two consecutive calls for proposals by the Euroregion New Aquitaine Euskadi Navarra. The objective of the project is to establish a common and functional biobank of human bile samples available for use in liquid biopsy and personalized medicine strategies to promote research in hepatobiliopancreatic diseases.

Drs. Carmen Berasain, María Arechederra and PhD student Carla Rojo are volunteers for science at the Spanish Association Against Cancer in Navarra and Alava. They participate in outreach activities (talks and experimental activities in schools, civic centers and congresses) in order to bring "the importance of cancer research" closer to society.

María Arechederra is founder and editor of the popular science blog Dciencia, which publishes 2-3 articles per month written by the editorial team or invited researchers from national and international scope. Members of Dr. Carmen Berasain's group participate regularly in Dciencia.

Scientific activity of the Hepatology Research Group: Carcinogenesis (HEPACAN)

Latest scientific publications