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AECC is funding a project led by Nabil Djouder to find treatments for the most common type of liver cancer

23.11.2021

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Nabil Djouder Nabil Djouder. /A. Tabernero. CNIO

The €300,000 project will study the molecular mechanisms that cause hepatocellular carcinoma to find new treatments for this disease

CNIO has also received 3 doctoral and one post-doctoral grant aimed at studying the cause of relapses in cancer patients and how to combat them or block metastasis

Since 2008, AECC has granted a total of 54 grants to CNIO, aimed at funding research into pancreatic cancer, childhood cancer, and brain metastases, among others

Nabil Djouder, lead researcher of the Growth Factors, Nutrients and Cancer Group at the Spanish National Cancer Research Centre (CNIO), is receiving funding from the Spanish Association Against Cancer (AECC) for the next three years to investigate hepatocellular carcinoma, one of the leading causes of cancer death, the most common and one of the most aggressive liver tumours. This funding, worth 300,000 euros, is part of AECC’s call for General Projects to support high-quality cancer research projects with a clear translational focus.

In 2021, CNIO also received three predoctoral and one postdoctoral grant from AECC to study the cells responsible for cancer relapses in order to alleviate this major problem facing many patients; to find combination therapies that improve efficacy and decrease the risk of relapse in patients with breast cancer; to develop therapies that block metastatic cells; and to block early metastases in melanoma.

Since 2008, AECC has granted a total of 54 grants to CNIO, aimed at funding research into different types of cancer, or oncological processes such as pancreatic cancer, childhood cancer, and brain metastases, among others.

Studying liver cirrhosis to fight liver cancer

Hepatocellular carcinoma is the most common and one of the most aggressive liver tumours. Although it is one of the leading causes of cancer death, there are no effective treatments against it.

There are several risk factors for this type of tumour, such as excessive alcohol consumption, obesity, a sedentary lifestyle, viral infections caused by hepatitis B or C, and drug use, among others. These factors cause liver damage, which the organ itself tries to repair, creating a series of scars that lead to liver cirrhosis.

In turn, cirrhosis can progress to liver cancer. “Liver cirrhosis is a risk factor for hepatocellular carcinoma,” says Djouder. “Up to 5% of patients with cirrhosis develop hepatocellular carcinoma, and about 80% of patients with liver cancer present a cirrhotic liver.” 

This relationship between liver cirrhosis and hepatocellular carcinoma may provide clues for better treatments to reduce mortality of this type of cancer. With the help of this project, Djouder’s laboratory will study the molecular mechanisms responsible for the progression of cirrhosis to cancer to develop new drugs or treatments that prevent or reduce its incidence. “This way, we will be able to improve the life expectancy of patients suffering from this type of cancer,” explains the researcher.

Avoiding relapse or stopping cancer metastasis 

In 2021, AECC also granted one postdoctoral and 3 predoctoral grants to young researchers Miguel Ruiz, of the Cell Division and Cancer Group led by Marcos Malumbres; Juan Garcia-Agullo, of the Microenvironment and Metastasis Group led by Héctor Peinado; Lydia Thelma Poluha of the Melanoma Group led by Marisol Soengas; and Karla Santos of the Growth Factors, Nutrients and Cancer Group led by Nabil Djouder, respectively.

Breast cancer is one of the most frequently diagnosed tumours in the world. CDK4 and CDK6 protein inhibitor-based therapies have become a standardised treatment in certain types of metastatic breast cancer, and “although they show very good results, they have certain limitations mainly due to the development of resistance mechanisms months after treatment,” notes Miguel Ruiz. The researcher will look for combined therapies that improve efficacy and decrease the risk of relapse in these patients.

Juan Garcia-Agullo will study and characterise the cells that initiate metastasis, which cause most cancer deaths. “So, the study and characterisation of these cells is essential to understanding metastasis and developing new therapies that fight it. In this project, we are analysing the development of new therapies against these cells and will analyse their use as therapy in melanoma and oral carcinoma.” 

Lydia Thelma Poluha will investigate melanoma, a tumour in which lesions as tiny as 1mm deep can trigger metastases. Poluha will use the ‘MetAlert’ mouse model, developed by the laboratory itself, which will allow her to visualise in vivo how melanomas act remotely before forming metastases. Her objective will be to study the mechanisms by which melanoma acts remotely to expand to block these processes.

Karla Santos will investigate latent or low proliferation tumour cells, which remain intact and undetectable after radiation therapy or chemotherapy treatments and cause relapse in patients. This research, using genetically modified mouse models, “will allow us to design new cancer therapeutic strategies to prevent patient relapse, which is the main problem they face after treatment.”

Finally, thanks also to the AECC funding awarded, this past summer CNIO welcomed several university students who carried out internships to complete their academic training: Ismael Nizialek spent his placement with the Cancer Immunity Group led by Maria Casanova; Mario Lopez worked with the Genomic Instability Group led by Oscar Fernandez-Capetillo; Santiago Barber with the Epithelial Carcinogenesis Group led by Paco Real; and Teresa Marti with the Transformation and Metastasis Group led by Eva Gonzalez Suarez.

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