Hypoxia in tumors: a paradigm for the approach to biochemical and physiologic heterogeneity.

While the inherent radiosensitivity of tumor cells is likely to affect treatment outcome, the biochemical and physiologic state of the cell may have a major impact. Tumors are likely to be highly heterogeneous for these dynamic properties. Hypoxic cells are radioresistant, requiring two to three times the radiation dose to kill them compared to the same cells in a eu-oxic state. Hypoxia can be of two types: 1) chronic hypoxia, which is diffusion limited, and 2) acute hypoxia, which is perfusion limited. The mechanism of and approaches toward these are different and can serve as a model for other biochemical and physiologic processes that may affect treatment outcome.