Does liver cancer have an Achilles heel?

This research will look at liver cancer in a new way to establish what happens in cells when diet-induced liver damage leads to liver cancer

  • Topic: Liver cancer
  • Institution: Institute for Research in Biomedicine
  • Country: Spain
  • Status: Ongoing
Researcher: Raul Mendez
  • Grant awarded: November 2020

I’m very grateful to the World Cancer Research Fund for this grant, it covers new and largely unexplored angles in liver diseases. It will allow us to identify new therapeutic targets in obesity-driven liver cancer. In the Translational Control of Cell Cycle and Differentiation lab at IRB Barcelona, we focus our research in the gene expression regulation mediated by the CPEB proteins, which play key roles in a variety of diseases, including autism, breast cancer and fatty liver. Our findings indicate that these proteins are responsible for the metabolic reprogramming that takes place in obesity and that could promote cell malignancy.

– Raul Mendez


Liver cancer is among the deadliest cancers worldwide and its prevalence is dramatically increasing due to the global epidemic of obesity and overweight. A liver transplant currently represents the only chance of long-term survival for patients with liver cancer. However, this procedure is highly expensive and many patients die on the waiting list due to donor organ shortage.

In addition, many patients are also considered ineligible for a liver transplant because of other conditions they have, such as obesity. New treatment options are therefore urgently required to reduce the burden of liver cancer worldwide. So it is essential to better understand the molecular and cellular causes linking obesity and liver cancer.

Aims and objectives

Although most liver cancers develop from chronic liver damage, studies mainly focus on its endpoint and rarely look at the evolution from early stages of the disease. In this project, we aim to explore the progression of the disease, from chronic liver damage caused by diet to the development of cancer. To do this, we will explore a possible new “Achilles heel” of cancer.

Tumours in obesity-driven liver cancer can overrule the genes that are involved in normal liver functions, causing them to instead promote its own growth. If we can understand this, we can use it against the cancer, opening a new window of opportunity to treat liver cancer and set the basis for new drug development strategies.

How it will be done

Currently, most of our knowledge about liver cancer comes from transcription – this is the process by which DNA is read and copied so that each cell in the body knows what its function is and what to do. We will instead be looking at what happens in the cell post-transcription.

This will advance our understanding of not only liver cancer tumours but also of the dynamic interplay between the tumour and its cellular surroundings in the body. It will also help us understand what happens in the body and cells before the tumour is formed, such as how fatty liver disease progresses to liver cancer.

Importantly, we will be using data from men and women.

Potential impact

This project will generate new knowledge, novel ideas for treatment, and strategies to reduce the incidence, morbidity and mortality of liver cancer. It will also improve patients’ quality of life and pave the way for future targeted prevention recommendations.