an important inhibitor for fighting tumors identified? · Inserm, science for health

Towards a new treatment · Inserm, science for health

Renaud Dentin is a researcher at the Cochin Institute (Department). Insert 1016 / CNRS / Paris Cité University) in Paris. With his colleagues, he has just demonstrated the involvement of a certain protein in the proliferation of liver cancer tumor cells. carcinoma hepatocellular. The results were published this week in Nature communicationidentify an inhibitor that could make it possible to better combat this tumor, but also other types of cancer such as breast cancer.

The context

THE hepatocellular carcinoma (HCC) is the most common type of liver cancer, but has limited treatment options. The best treatment is removal through surgery. However, in cases where this disease is only recognized late, this is not enough and the drug route is then preferred. Almost all current clinical trials focus on immunotherapy, a therapy that harnesses the immune system, but 60 to 70% of patients are still resistant to it. Therefore, it seems important to identify the factors that influence this response to treatments.

We know that cancer cells have a specific metabolism that adapts to their increased energy needs, with their rapid proliferation requiring significant energy expenditure compared to normal cells. Targeting these specific metabolic processes could therefore represent a potential approach to limiting the proliferation of cancer cells. In recent years, various molecules have been evaluated from this perspective.

In this context, Renaud Dentin and his team carried out a research project financially supported by Inserm, the ARC Foundation, the League against Cancer, the City of Paris (Émergence Project), Europe (through an ERC Starting Grant) and the CNRS and the University of Paris Cité. The goal: to determine the role of a specific protein factor of transcription ChREBP (Carbohydrate Responsive Element Binding Protein) in the initiation and development of hepatocellular carcinoma.

The results

Using information collected from 1,500 HCC patients and 10 different cohorts, the scientists showed a systematic increase in ChREBP protein expression in tumors compared to non-tumor cells. In these different human cohorts, it was observed that patients with high expression of ChREBP in their tumor had a lower life expectancy compared to patients with low expression of the protein. These data provide the first experimental evidence in humans for a possible role of ChREBP in the mechanisms of hepatocellular carcinoma initiation and development.

The research team then managed to identify the first pharmacological inhibitor of ChREBP that would be able to slow the growth of cancer cells by blocking certain actions important for their development. Significantly, this inhibitor has been observed to increase the effectiveness of an existing cancer treatment. Sorafenib, which blocks signals that promote the growth of cancer cells. In addition, this inhibitor would also have promising prospects in the treatment of other types of cancer such as breast cancer, colon cancer and leukemia.

Perspectives

This type of basic research is of great importance: it makes it possible to understand the mechanisms behind the development of cancer and the mechanisms of action of new molecules. This is essential for initiating projects translational research located between basic research and clinical research, the aim of which is to evaluate the effectiveness and tolerability of new treatments in patients. These research projects play an important role in the fight against social and environmental scourges such as cancer.

This study therefore presents the first pharmacological inhibitor identified for ChREBP, which could become a key tool in the treatment of HCC. Its potential as a new therapeutic agent could ultimately lead to a process of pharmacological optimization and valorization.