Abstract
Poor vascularization resulting in the inadequate supply of nutrients (oxygen, glucose) and/or removal of catabolites (lactic acid) may produce regions of nutrient deprivation within solid tumours (Thomlinson and Gray, 1955; Tannock, 1968). Cells in a hypoxic microenvironment become dependent on glycolysis for energy metabolism. The resulting lactic acid production coupled with ATP hydrolysis may lead to the development of acidic conditions (Hochachka and Mommsen, 1983). It has been shown that the mean pHe1 within both human and murine tumours (typically in the range 6.5–7.0) is on average 0.5 units lower than that of normal tissue (Wike-Hooley et al, 1984. Hypoxic cells are resistant to radiation therapy and many anti-cancer drugs have limited penetration into tissue and/or have limited activity against slowly proliferating cells situated distant from blood vessels. Thus, cells in nutrient deprived regions of solid tumours may be responsible for the failure of conventional therapy (Sutherland et al, 1982; Tannock, 1982). A major objective of our studies is to develop new therapeutic strategies which may utilize the acidic conditions within solid tumours to selectively kill nutrient-deprived cells.
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© 1989 Springer-Verlag Berlin Heidelberg
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Newell, K., Tannock, I. (1989). Carbonylcyanide-3-Chlorophenylhydrazone A Prototype Agent for the Selective Killing of Cells in Acidic Regions of Solid Tumours. In: Evangelopoulos, A.E., Changeux, J.P., Packer, L., Sotiroudis, T.G., Wirtz, K.W.A. (eds) Receptors, Membrane Transport and Signal Transduction. NATO ASI Series, vol 29. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74200-2_26
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DOI: https://doi.org/10.1007/978-3-642-74200-2_26
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