A new computational model allows identifying new therapeutic targets to attack cancer cells by making their pH more acidic. The study is the result of the joint work of the Moffitt Cancer Center and the University of Maryland and has been published in Nature Communications.
Cancer cells cause the acidification of their environment and consequently the cells alkalize inside. This deregulation should be a problem for the development and proliferation of cells; nevertheless, in cancer, the opposite occurs.
A computational study, co-authored by computational chemist Miquel Duran-Frigola, from the Institute of Biomedical Research (IRB Barcelona), shows that cancer cells proliferate less and less strongly when their internal pH is acidified, a discovery that may result in a new therapeutic approach.
Using tens of thousands of historical data from biochemical papers and a database of gene expression of cancer cells, the researchers have developed a computational model that analyzes how the activity of almost 2,000 metabolic enzymes is affected by variations in pH.
“We are a computational laboratory and we are dedicated to biology systems. We wanted to address the problem on a large scale, “says Duran-Frigola, associate researcher at the Laboratory of Structural Bioinformatics and Network Biology , led by Patrick Aloy, researcher at the Catalan Institution for Research and Advanced Studies (ICREA).
“Understanding the connection between metabolic pathways that work best at different pHs can give us insights into the mechanisms that cancer uses to survive in its basic pH conditions,” explains Duran-Frigola.
The researchers have confirmed the hypothesis that was initially raised: if cancer cells proliferate comfortably with alkaline pH levels, then they would be more sensitive to acidic pH. This opens the door to consider the acidification of the inside of cancer cells, combined with conventional cancer therapies, as a good therapeutic strategy.
New therapeutic targets
In addition, the reserachers have been able to identify the metabolic enzymes that make synergy with intracellular acidity in the development of cancer, making them possible therapeutic targets. Five of those potential targets have been tested in the laboratory in breast cancer cell lines, showing promising results.
“This work is still very academic, but we believe that some of the identified targets are ready to be tested on animals and move on to more advanced pre-clinical stages,” says Miquel Duran-Frigola.