Research News
Modeling Tumor Response to Acidity Changes Predicts New Therapeutic Options
A well-known characteristic of tumors is that they increase the acidity of their surroundings, which makes it easier for them to spread beyond their initial bounds. Over the past few years, researchers have obtained data from animal studies suggesting that manipulating the extracellular acidity near tumors could prevent metastases from developing and therefore prolong patient survival. Now, researchers have theoretical support for this idea in the form of a mathematical model that shows how the body's acidity, or pH, buffering system functions and how it can be manipulated to change the extracellular pH near tumors.
Reporting its work in the journal Mathematical Biosciences, a research team headed by Natasha Martin of Oxford University and Robert Gatenby and Robert Gillies of the H. Lee Moffitt Cancer Center & Research Institute Physical Sciences-Oncology Center, described the relatively simple but realistic model of the bicarbonate/carbon dioxide buffering system that the body uses to maintain a near-constant extracellular pH. Using data from mice and humans, the investigators demonstrated that this model accurately simulates blood pH in both normal and diseased states. The research team then used the model to predict that raising the extracellular pH, by administering sodium bicarbonate - baking soda - should both promote the survival of healthy cells and reduce the ability of tumor cells to invade surrounding tissues.
Next, the investigators used the model to explore various ways of normalizing extracellular pH. One approach that might work would adjust the kidney's ability to secrete acid, but this type of treatment would impact the pH of the entire blood stream and therefore requires caution. Another approach, which would likely be safer to implement, would be to reduce the ability of tumors to produce acid. The researchers are now exploring several ways of achieving that reduction.
This work, which is detailed in a paper titled, "A mathematical model of tumour and blood pHe regulation: the HCO-3/CO2 buffering system," was supported by the National Cancer Institute's Physical Sciences in Oncology initiative, a program that aims to foster the development of innovative ideas and new fields of study based on knowledge of the biological and physical laws and principles that define both normal and tumor systems. An abstract of this paper is available at the journal's Web site.
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