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Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression

Saxena, Kritika and Jolly, Mohit Kumar (2019) Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression. In: BIOMOLECULES, 9 (8).

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Official URL: https://dx.doi.org/10.3390/biom9080339


Hypoxia has been shown to increase the aggressiveness and severity of tumor progression. Along with chronic and acute hypoxic regions, solid tumors contain regions of cycling hypoxia (also called intermittent hypoxia or IH). Cyclic hypoxia is mimicked in vitro and in vivo by periodic exposure to cycles of hypoxia and reoxygenation (H-R cycles). Compared to chronic hypoxia, cyclic hypoxia has been shown to augment various hallmarks of cancer to a greater extent: angiogenesis, immune evasion, metastasis, survival etc. Cycling hypoxia has also been shown to be the major contributing factor in increasing the risk of cancer in obstructive sleep apnea (OSA) patients. Here, we first compare and contrast the effects of acute, chronic and intermittent hypoxia in terms of molecular pathways activated and the cellular processes affected. We highlight the underlying complexity of these differential effects and emphasize the need to investigate various combinations of factors impacting cellular adaptation to hypoxia: total duration of hypoxia, concentration of oxygen (O-2), and the presence of and frequency of H-R cycles. Finally, we summarize the effects of cycling hypoxia on various hallmarks of cancer highlighting their dependence on the abovementioned factors. We conclude with a call for an integrative and rigorous analysis of the effects of varying extents and durations of hypoxia on cells, including tools such as mechanism-based mathematical modelling and microfluidic setups.

Item Type: Journal Article
Publisher: MDPI
Additional Information: The copyright for this article belongs to MDPI
Keywords: cyclic hypoxia; intermittent hypoxia; obstructive sleep apnea; HIF-1 alpha signaling; acute hypoxia; chronic hypoxia; mathematical modeling
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Date Deposited: 16 Oct 2019 10:18
Last Modified: 16 Oct 2019 10:18
URI: http://eprints.iisc.ac.in/id/eprint/63653

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