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[OA article] Scientists Define a New Mechanism Leading to Tumor Hypoxia

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Growing evidence from experimental studies and clinical trials suggests a fundamental role of hypoxia in solid tumors.  The mechanisms leading to hypoxia include the rapid rate of tumor growth, poor tumor perfusion or transiently disrupted tumor blood flow.  Now, scientists from the University of Pennsylvania, led by Professor Cameron J. Koch, have discovered a previously uncharacterized mechanism that contributes to – and may influence –  the temporal and spatial distribution of tumor hypoxia.

Hypoxic cancer cells represent the most aggressive type of a tumor. In case of malignant tumors they tend to be resistant to radio therapy, and low oxygen concentration can actually enhance metastasis. Thus, hypoxia – labeled accordingly as a poor prognostic factor – is emerging as an important, high-priority target for cancer therapy.

So far, there have been two recognized forms of tumor hypoxia: Diffusion limited hypoxia occurs as a result of distance from vessels; it is a stable factor and it occurs at a scale of hundreds of microns. Perfusion limited hypoxia, in contrast, results from perturbations in tumor blood flow, which can be both transient and recurring, but it also generally occurs on a smaller scale. The current report demonstrates that in addition to these two mechanisms, there is a stable gradient of oxygen that can occur over multi-millimeter distances along the length of a tumor vessel leading to hypoxia at the more distal portions of the vessel.  This finding leads to a more complete understanding of the factors that have an influence on tumor oxygenation – adding a third mechanism that contributes to tumor hypoxia and would be expected to scale with tumor size.

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