Dr. Antoni Esteve Foundation Research Award 2021
C. de Melchor Fernández Almagro, 3
In 2019, a group from the Centro Nacional de Investigaciones Cardiovasculares published in the journal Nature relevant data around the involvement of the p38gamma protein in the development of the main type of primary liver cancer. This is hepatocellular carcinoma, which affects more than one million people a year worldwide and for which few pharmacological options are currently available.
The international tribunal that awards the Dr. Antoni Esteve Foundation Research Award has considered this scientific article as the most important pharmacological publication published by a Spanish author between 2019 and 2020. Antonia Tomás Loba, first author of the article, and Guadalupe Sabio, director of the group, received this award on 19 d October 2021 in the CNIC Auditorium, where was Dr. Vicente Andrés, Director of Basic Research at the CNIC, and Dr. Fèlix Bosch, Director of the Dr. Antoni Esteve.
The article p38γ is essential for cell cycle progression and liver tumorigenesis not only discovers how the p38gamma protein is related to cell division in the liver but has also studied in mice what happened when they were chemically induced by liver cancer with or without this protein. “Whether this protein was missing or its activity was blocked with a drug, we managed to delay the development of the tumor,” says Tomás Loba. “These results could be extrapolated to people, as we have seen that p38gamma is increased in human samples from liver cancer patients,” says Guadalupe Sabio, director of this CNIC research group.
“This discovery is of great medical importance because it identifies p38gamma as a promising target for the treatment of liver cancer. The results were obtained using an excellent combination of pharmacological and genetic approaches to study the role of p38gamma. The analysis was performed using cutting-edge technologies in cell and molecular biology, imaging and computational biology, ”explains Sabine Werner, of the Federal Polytechnic School in Zurich and a member of the jury for the Dr. Antoni Esteve together with Xavier Guitart, from the National Institute of Drug Abuse in the United States, and Fèlix Bosch, director of the Dr. Antoni Esteve.
“The study, therefore, makes a fundamental contribution to our understanding of the progression of the cell cycle in diseased liver and regeneration and opens new avenues for the treatment of liver cancer,” concludes Sabine Werner.
The CNIC team has been studying a family of proteins, p38 kinases, for several years, which are activated when cells experience any type of stress. “Studying in detail the three-dimensional structure of proteins, we observed that one of them, p38gamma, was very similar to that of another group of proteins known as CDKs. The latter – says Sabio – have been known for a long time to be related to the development of cancer “.
In studies in the laboratory in collaboration with scientists from the National Center for Oncological Research (CNIO) and Silvia Osuna, a researcher at the University of Girona, they delved into these similarities with CDKs. Thus, they found that a known inhibitor of CDK2, perfenidone, also decreased p38gamma activity. In this way, using the inhibitor blocked its activity and exerted a tumor-suppressing action.
In collaboration with the University Hospital of Salamanca, this CNIC group has also found that the amount of this protein in the liver increases with liver fibrosis. A condition that precedes cancer and is much higher in patients with liver cancer. “In the future, this type of cancer could be treated with a drug that specifically inhibits p38gamma,” the researchers suggest. “The advantage over other pathways is that our results suggest that inhibition of p38gamma would not affect other proliferating tissues such as the intestine or hair,” they add.
The members of the international jury of the Dr. Antoni Esteve also wanted to recognize with an honorable mention the article published in 2019 in the journal Nature Metabolism by the group of the Instituto de Investigación Sanitaria de Santiago and the University of Santiago de Compostela, coordinated by Rubén Nogueiras and Luisa Seoane, in which they discover the mechanism by which some drugs used for the treatment of other diseases also decrease body weight. This honorable mention is added to the Dr. Foundation Research Award. Antoni Esteve who already received the Nogueiras team in 2017 to demonstrate the effectiveness of a drug for diabetes in weight reduction.
This is the seventeenth edition of the Dr. Foundation Research Award. Antoni Esteve, which is awarded to the best work in pharmacology published by a Spanish author in the last two years in any of its aspects (design, synthesis, galenic development, clinical or laboratory evaluation, use, etc.).
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