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Inhibition of p38 reduces the growth of lung tumours

20 Jan 20

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Ángel Nebreda’s team has published a study in the journal PNAS reporting the involvement of the protein p38 in the progression of lung cancer.

The work shows that patients with low levels of this protein have a better prognosis. 

One of the biggest challenges faced by biomedicine is the development of more selective and efficient cancer treatments.

In 2018, 1.7 million people died from lung cancer worldwide, a number equivalent to the population of Barcelona. The high mortality rate of lung cancer reflects the need for the development of treatments that are more efficient. 

A study headed by Ángel R. Nebreda, ICREA researcher and head of the Signalling and Cell Cycle Lab at the Institute for Research in Biomedicine (IRB Barcelona) and published in the journal PNAS demonstrates that the protein p38 is one of the key elements supporting lung cancer growth. In particular, the study focuses on cells expressing the oncogene Kras, which causes the transformation of a healthy cell into a cancer cell and whose mutations are responsible for approximately 25% of lung cancer cases.  

For this study, the scientists have used genetic mouse models that develop lung tumours with the KrasG12V mutation. Using these models, they have observed that p38 inhibition leads to a dramatic reduction in tumour growth and aggressiveness. Furthermore, complementary studies performed with information deposited in cancer genome databases indicate that the patients with lower levels of p38 in tumours have a more favourable prognosis. This function of p38 is related to the production of factors that stimulate cancer cell division and thus enhance tumour growth. 

The relevance of this work lies in the fact that “it shows how tumours exploit a protein, which in principle protects healthy lung cells, for their own progression,” says Jessica Vitos, first author of the paper. The result of this study may find therapeutic application. In this regard, “Chemical compounds that inhibit p38 function would interfere with the growth of lung cancer cells,” she explains.

The study has been funded by the European Research Council (ERC), the Spanish Ministry of Science, Innovation and Universities (MICINN), the Catalonian Agency for Management of University and Research Grants (AGAUR), and the BBVA Foundation.

The work has been conducted in collaboration with Dr. Mariano Barbacid’s group at CNIO, Madrid, and with Dr. Alberto Villanueva at IDIBELL, L’Hospitalet de Llobregat.

 

Reference article

Jessica Vitos-Faleato, Sebastián M. Real, Nuria Gutierrez-Prat, Alberto Villanueva, Elisabet Llonch, Matthias Drosten, Mariano Barbacid, Angel R. Nebreda, 

Requirement for epithelial p38α in KRAS-driven lung tumor progression 

PNAS (2020) DOI: 10.1073/pnas.1921404117

 

 

About IRB Barcelona

Created in 2005 by the Generalitat de Catalunya (Government of Catalonia) and University of Barcelona, IRB Barcelona is a Severo Ochoa Centre of Excellence, a seal that was awarded in 2011. The institute is devoted to conducting research of excellence in biomedicine and to transferring results to clinical practice, thus improving people’s quality of life, while simultaneously promoting the training of outstanding researchers, technology transfer, and public communication of science. Its 27 laboratories and eight core facilities address basic questions in biology and are orientated to diseases such as cancer, metastasis, Alzheimer’s, diabetes, and rare conditions. IRB Barcelona is an international centre that hosts 400 employees and more than 30 nationalities. It is located in the Barcelona Science Park. IRB Barcelona is a CERCA center, and a member of the Barcelona Institute of Science and Technology (BIST).