A new study focusing on the environment inside cancer cells may lead to new targeted treatment strategies. Researchers suggest that lowering the pH inside cancer cells to make it more acidic can slow down the growth and spread of the disease, and possibly provide new options for treatment. Their results were published in Nature Communications.
"We see the alkaline pH of cancer cells as an evolutionary advantage. To exploit it, we designed a system biology approach to harness this as a targetable vulnerability against cancer cells," said co-first author on this study.
Cancer cells have the ability to adapt and change their metabolism in order to survive, grow and reproduce. The research team, which included a computer scientist, bioinformatics expert, tumor biologist and cancer metabolism scientist, utilized data from previous biochemical assays and a database on the gene expression of cancer cells to develop a computational model that analyzes how variations in pH affect the activity of nearly 2,000 metabolic enzymes.
"If we can better understand how the metabolism works in different pH environments, we can determine the changes cancer cells make to survive and grow," said senior member of the study.
The researchers found that cancer cells proliferate more with an alkaline intracellular pH, making them more vulnerable under acidic pHi. They show that in silico, alkaline pHi maximizes cancer cell proliferation coupled to increased glycolysis and adaptation to hypoxia (i.e., the Warburg effect), whereas acidic pHi disables these adaptations and compromises tumor cell growth.
They also identified the metabolic enzymes (GAPDHand GPI) that have their highest activity under alkaline pHi during the development of cancer, which can now be used as possible therapeutic targets.
"We have already tested five of these potential targets using breast cancer cell lines and had positive results," said the co-first author. "While more research is needed in the pre-clinical trial setting, this study provides us with a promising new therapeutic strategy."
Lowering pH inside cells may put the brakes on cancer growth
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