A research group of the National Center for Cardiovascular Research (CNIC), coordinated by Guadalupe Sabio, has spent several years studying a family of proteins, p38 kinases, which are activated when the cells undergo any kind of stress. The team discovered that one of the four existent p38 kinases, p38ɣ plays a key role in the beginning of cell division of liver cells.
Based in this finding, published this week in the journal Nature, Sabio said that p38ɣ “can be a good therapeutic target for liver cancer.”
Inhibition of p38ɣ to treat liver cancer
“Studying in detail the three-dimensional structure of proteins, we observed that one of them was very similar to that of another group of proteins known as CDKs. The latter, Sage said, 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 studied the similarities with the CDKs.
The scientists observed that a known inhibitor of CDK2 also decreases the activity of p38ɣ, and a tumor suppressor action was exerted. To check if p38ɣ was really involved in cell division, Antonia Tomás-Loba, first author of the article, analyzed what happened when chemically induced liver cancer in mice with or without this protein.
The results were really promising: “in both, if this protein was missing or if its activity was blocked with a drug, we managed to delay the development of the tumor,” said Tomás-Loba.
“These results could be extrapolated to people,” Sabio added.
In collaboration with the University Hospital of Salamanca, the researchers 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 p38ɣ,” the researchers suggest.
“The advantage over other pathways is that our results suggest that the inhibition of p38ɣ would not affect other tissues that are in constant proliferation such as the intestine or hair,” they added.