Non-constant tumour blood flow--implications for therapy.

In the past few years, 'perfusion-limited' hypoxia caused by intermittent decreases in tumour blood flow has received increasing attention. Little effort, however, has gone into characterizing the nature, magnitude or duration of these changes, or their functional significance other than as modifiers of radiotherapy. We have therefore undertaken multiple, quantitative analyses of tumour blood flow in human tumour xenograft systems, and rigorously examined the ramifications of transient blood flow changes. Tumour blood flow in these experimental tumours is much less constant than has previously been assumed, and not only impacts on response to radiotherapy and chemotherapy, but also on the more fundamental processes of tumour growth and repopulation. Notably, responses entirely consistent with the laboratory results have been seen in our initial studies of human tumours sequentially biopsied during treatment.