Eco-evolutionary causes and consequences of temporal changes in intratumoural blood flow.

Temporal changes in blood flow are commonly observed in malignant tumours, but the evolutionary causes and consequences are rarely considered. We propose that stochastic temporal variations in blood flow and microenvironmental conditions arise from the eco-evolutionary dynamics of tumour angiogenesis in which cancer cells, as individual units of selection, can influence and respond only to local environmental conditions. This leads to new vessels arising from the closest available vascular structure regardless of the size or capacity of this parental vessel. These dynamics produce unstable vascular networks with unpredictable spatial and temporal variations in blood flow and microenvironmental conditions. Adaptations of evolving populations to temporally varying environments in nature include increased diversity, greater motility and invasiveness, and highly plastic phenotypes, allowing for broad metabolic adaptability and rapid shifts to high rates of proliferation and profound quiescence. These adaptive strategies, when adopted in cancer cells, promote many commonly observed phenotypic properties including those found in the stem phenotype and in epithelial-to-mesenchymal transition. Temporal variations in intratumoural blood flow, which occur through the promotion of cancer cell phenotypes that facilitate both metastatic spread and resistance to therapy, may have substantial clinical consequences.