The effect of therapy on tumour vascular function.

It has been established that malignant tissue as a consequence of abnormal morphogenesis has a structurally abnormal blood supply. These structural and as a consequence functional differences between normal and neoplastic vasculature provide a basis for selective modulation of tumour vascular function. Agents have been identified which can induce both irreversible and reversible effects on tumour blood flow. Hyperthermia, photodynamic therapy, tumour necrosis factor and flavone acetic acid are known to elicit most of their anti-tumour effect via irreversible changes in tumour vascular function. In addition to the extensive tumour cell kill and thus therapeutic potential provided by such chronic modulation of blood flow, acute transient changes in macroregional and microregional tumour blood flow could also play an important role if used appropriately with conventional therapies. The use of this latter type of modulation is discussed with reference to known examples of such 'vasoactive' compounds. It is also emphasized that blood flow changes induced in tumour tissue can be a 'double-edged sword' with detrimental consequences for therapeutic outcome if inappropriate changes are induced, for example, reductions in flow at the time of conventional radiotherapy or chemotherapy by agents not considered to be 'vasoactive'. To emphasize this point examples of blood flow modulation by pimonidazole and cis-platinum, agents that are used in conjunction with radiotherapy, are described.