Abstract

The tumour microenvironment is complex and heterogeneous in terms of cellular composition, pathophysiology and structure. It is also dynamic, changing in response to physical and chemical stimuli, including therapy. Gaining a greater understanding of how microenvironmental components within a tumour change in response to therapy can give rise to key therapeutic opportunities. A classical example here is that tumours reoxygenate during fractionated radiotherapy, increasing the proportion of the tumour readily killed by radiation treatment. For a molecular targeted therapy example, vascular endothelial cells activate signalling pathways making them more sensitive to small molecule inhibitors of the vascular endothelial growth factor receptor.  An overriding pathophysiological condition in tumours likely to impact on all aspects of the microenvironment is hypoxia. From a radiation perspective, hypoxia directly causes tumour cell radioresistance but will further influence overall response as hypoxia mediated changes in protein expression influence complex interactions between tumour and host cells within the microenvironment. This “foe” can be targeted in many ways. Of interest is whether we are coincidentally manipulating other aspects of the tumour microenvironment towards a more opportunistic state for additional therapies, and if so, which ones.