Inhibition of p38 reduces the growth of lung tumours

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