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Review

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

Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India
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Biomolecules 2019, 9(8), 339; https://doi.org/10.3390/biom9080339
Received: 18 July 2019 / Revised: 31 July 2019 / Accepted: 1 August 2019 / Published: 3 August 2019
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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 (O2), 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. View Full-Text
Keywords: cyclic hypoxia; intermittent hypoxia; obstructive sleep apnea; HIF-1α signaling; acute hypoxia; chronic hypoxia; mathematical modeling cyclic hypoxia; intermittent hypoxia; obstructive sleep apnea; HIF-1α signaling; acute hypoxia; chronic hypoxia; mathematical modeling
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MDPI and ACS Style

Saxena, K.; Jolly, M.K. Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression. Biomolecules 2019, 9, 339. https://doi.org/10.3390/biom9080339

AMA Style

Saxena K, Jolly MK. Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression. Biomolecules. 2019; 9(8):339. https://doi.org/10.3390/biom9080339

Chicago/Turabian Style

Saxena, Kritika, and Mohit K. Jolly 2019. "Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression" Biomolecules 9, no. 8: 339. https://doi.org/10.3390/biom9080339

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