Health Spain , Salamanca, Monday, June 09 of 2014, 19:09

The inhibition of a family of proteins helps to fight chronic myeloid leukemia

A team of researchers of IBSAL has found a new therapeutic target cell, a discovery that may help to develop a complementary therapy to the current one, according to a work published at ‘Clinical Cancer Research’

JPA/DICYT A team of researchers of Biomedical Research Institute of Salamanca (IBSAL) has identified a family of proteins called NADPH oxidases that could be a good therapeutic target cell to fight chronic myeloid leukemia. Even though this type of cancer is caused by an oncoprotein for which there are treatments already, until now, scientists have been able to control the disease, but not heal it. They think that combining the existing therapy with inhibitors of this family of proteins will produce good results, just like cellular cultures and animal models have already confirmed.

“We have seen that when we inhibit this type of protein, chronic myeloid leukemia cells do not proliferate and die in ‘in vitro’ as well as in animal models; therefore, it is a preclinical study”, Ángel Hernández has explained to DiCYT. He is a scientist of the research group ROS in Hematopoiesis, named this way because it studies the role of the Oxygen reactive species (known as oxygen free radicals) in hematopoiesis, the blood cell formation process.

The results of this work, which lasted for more than four years, have just been published in the scientific magazine Clinical Cancer Research and have confirmed that NADPH oxidases have an important role in cancer, since the team of the University Hospital of Salamanca was making this leukemia research at the same time that other groups have been publishing similar results in solid tumors. “These enzymes are good supporting actors in tumors and our work demonstrates that if we eliminate the movie leading actor and the supporting actor, the movie is ruined”, the researcher comments.


Therefore, the scientists consider that the most important information of the study is that when one combines the current therapy with the inhibition of this family of proteins, the effects are stronger. Besides, normal cells would not be so affected by this combined action, since they do not express the oncoprotein which originated the illness. That is, the result of this combination of drugs would be a very specific treatment against tumor cells.

This family of proteins has a physiologic function in normal cells, they are specialized in the production of oxygen free radicals, but its activity is increased in cancer cells. In fact, the same research group has confirmed that it also carries out a task in another type of leukemia, the chronic myeloid leukemia.


Disease Paradigm with a definite molecular target cell


“The chronic myeloid leukemia is the disease paradigm that has started being treated with a definite molecular target cell; it has an oncogenic protein to which the tyrosine kinase inhibitors are directed, which is very effective in controlling the disease”, the researcher Consuelo del Cañizo affirms. Nevertheless, “these inhibitors make the disease chronic, but they do not heal them, since it remains asleep and when the inhibitors are removed, it appears again”, she explains.


Consequently, nowadays, the researchers are looking for complementary treatments that may act in a synergic way with the tyrosine kinase inhibitors, and this progress is an important step to obtain it and reach the great objective: heal the disease and remove the treatment.

However, “Even now, we have a lot to do”, Del Cañizo points out, because, in spite of the good results in cell cultures and in animals, it is necessary to develop specific enzyme inhibitors which can be used in human beings. In that sense, she recalls that “the development of drugs is very difficult for a research group, the normal procedure would be that a company got interested and, in contact with us, tried to achieve effective and safe molecules”.


This type of leukemia occurs in 1 per 100,000 inhabitants every year. In the last years, the research advances have allowed three or four extra years of survival in an average of 10.

Without funding


Despite its success, this research team is currently without funding since December 2014, so that not only the future of this line of research is in danger, but also the research team, formed by between five and seven people because of the students who join up with and that, until now, have been able to develop this work thanks to the Economy and Competitiveness Ministry and the Castilla y León Council funding.

According to the researchers, the emerging research teams are the ones who have been suffering with the crisis, because they are not established yet and are formed by young members, in this case, Beatriz Sánchez Sánchez, the first name in the article and whose thesis this study is based on.




NADPH oxidases as therapeutic targets in chronic myeloid leukemia. Beatriz Sanchez-Sanchez, Sara Gutierrez-Herrero, Guillermo Lopez-Ruano,Rodrigo Prieto-Bermejo, Marta Romo-Gonzalez, Marcial Llanillo, Atanasio Pandiella, Carmen Guerrero, Jesus F. San Miguel, Fermin Sanchez-Guijo, Maria-Consuelo del Canizo and Angel Hernandez-Hernandez.
Clinical Cancer Research. May 15, 2014; doi:10.1158/1078-0432.CCR-13-3044