Biological Aspects of Hyperthermia: A Perspective on the Eve of the New Millennium

摘要

The main motivation for the study of the biology of hyperthermia in the last three decades has been the rekindled interest in the application of hyperthermia for the treatment of malignant tumours in the clinic, both as a stand-alone modality and in combination with radio- and chemotherapy. The large body of literature generated in this period underlies the biological rationale for the use of hyperthermia in the clinic. Heat kills cells in a predictable and repeatable way. The cell cycle variation in sensitivity to heat is opposite to that observed with ionising radiation, in that the S phase of the cell cycle, which is most resistant to the action of ionising radiation, is the most sensitive to hyperthermia. Hypoxic cells, which are resistant to ionising radiation, are not preferentially spared by hyperthermia; Indeed, under certain experimental conditions, hypoxic cells can be sensitised to heat. Cells in culture exposed to environmental conditions similar to that found in tumours, i.e. nutritionally deprived and at acid pH (<6.8), are sensitised to heat. Thus, although it appears that the malignant state per se does not affect heat sensitivity, the physiological state of tumours can predispose them to heat sensitivity . Furthermore, the poor vasculature of tumours results in the reduction of blood flow after hyperthermia. Exposure to hyperthermia leads to sensitisation to both ionising radiation and chemotherapeutic drugs. In the case of heat radiosensitisation and ionising radiation, it has been demonstrated that the sensitisation is due to the inhibition of the repair of both lethal and sublethal damage induced by radiation. Recent studies of the combination of three modalities, heat, drugs and radiation, are one of the topics covered in this symposium.