A number of studies have shown that the extracellular pH (pHe) in
cancers is typically lower than that in normal tissue and that an acidic pHe promotes invasive
tumor growth in primary and metastatic
cancers. Here, we investigate the hypothesis that increased systemic concentrations of pH
buffers reduce intratumoral and peritumoral
acidosis and, as a result, inhibit malignant growth. Computer simulations are used to quantify the ability of systemic pH
buffers to increase the acidic pHe of
tumors in vivo and investigate the chemical specifications of an optimal
buffer for such purpose. We show that increased serum concentrations of the
sodium bicarbonate (NaHCO(3)) can be achieved by ingesting amounts that have been used in published clinical trials. Furthermore, we find that consequent reduction of
tumor acid concentrations significantly reduces
tumor growth and invasion without altering the pH of blood or normal tissues. The simulations also show that the critical parameter governing
buffer effectiveness is its pK(a). This indicates that NaHCO(3), with a pK(a) of 6.1, is not an ideal intratumoral
buffer and that greater intratumoral pHe changes could be obtained using a
buffer with a pK(a) of approximately 7. The simulations support the hypothesis that systemic pH
buffers can be used to increase the
tumor pHe and inhibit
tumor invasion.