Adaptation to Stochastic Temporal Variations in Intratumoral Blood Flow: The Warburg Effect as a Bet Hedging Strategy
Abstract
While most cancers promote ingrowth of host blood vessels, the resulting vascular network usually fails to develop a mature organization, resulting in abnormal vascular dynamics with stochastic variations that include slowing, cessation, and even reversal of flow. Thus, substantial spatial and temporal variations in oxygen concentration are commonly observed in most cancers. Cancer cells, like all living systems, are subject to Darwinian dynamics such that their survival and proliferation are dependent on developing optimal phenotypic adaptations to local environmental conditions. Here, we consider the environmental stresses placed on tumors subject to profound, frequent, but stochastic variations in oxygen concentration as a result of temporal variations in blood flow. While vascular fluctuations will undoubtedly affect local concentrations of a wide range of molecules including growth factors (e.g., estrogen), substrate (oxygen, glucose, etc.), and metabolites ([Formula: see text], we focus on the selection forces that result solely from stochastic fluctuations in oxygen concentration. The glucose metabolism of cancer cells has been investigated for decades following observations that malignant cells ferment glucose regardles...Continue Reading
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