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.
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.
Proceedings of the National Academy of Sciences Jan 2020. doi: 10.1073/pnas.1921404117