Response of tumours to hyperglycaemia: characterization, significance and role in hyperthermia

The response of both neoplastic and surrounding normal tissue to hyperthermia is influenced by a number of physical, physiological, biological and immunological factors. Two physiological factors that play an important role are blood flow and pH. Temperature distributions within neoplastic and surrounding normal tissue during hyperthermia are influenced by convective heat transfer between the blood and tissue bed. A number of in vitro studies have illustrated that lowering media pH sensitizes cells to hyperthermia. It has been suggested that pharmacological agents could be used in conjunction with hyperthermia treatment to improve cancer treatment if these agents decrease tumour blood flow and/or decrease tumour pH. One agent that has been studied extensively for this purpose is glucose. The objective of this paper is to review the results on the effect of hyperglycaemia on normal and tumour tissue blood flow and pH and its role in hyperthermia. After a brief discussion of the role of tumour pH and blood flow in hyperthermia treatment, data available in the literature on the effect of hyperglycaemia on normal and tumour tissue blood flow and pH are reviewed. Finally, the role of hyperglycaemia in hyperthermia treatment is discussed, and various studies involving the combined treatment are summarized. Key unanswered questions and directions for future research are pointed out.