Hypoxic Radioresistance: Can ROS Be the Key to Overcome It?

Radiotherapy is a mainstay treatment for many types of cancer and kills cancer cells via generation of reactive oxygen species (ROS). Incorporating radiation with pharmacological ROS inducers, therefore, has been widely investigated as an approach to enhance aerobic radiosensitization. However, this...

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Bibliographic Details
Published in:Cancers 2019-01, Vol.11 (1), p.112
Main Authors: Wang, Hui, Jiang, Heng, Van De Gucht, Melissa, De Ridder, Mark
Format: Article
Language:English
Subjects:
Antioxidants
Apoptosis
Cancer
Detoxification
DNA damage
Free radicals
Homeostasis
Hypotheses
Hypoxia
Radiation therapy
Radioresistance
Radiosensitization
Reactive oxygen species
Review
Tumor cells
Tumors
X-rays
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Summary:Radiotherapy is a mainstay treatment for many types of cancer and kills cancer cells via generation of reactive oxygen species (ROS). Incorporating radiation with pharmacological ROS inducers, therefore, has been widely investigated as an approach to enhance aerobic radiosensitization. However, this strategy was overlooked in hypoxic counterpart, one of the most important causes of radiotherapy failure, due to the notion that hypoxic cells are immune to ROS insults because of the shortage of ROS substrate oxygen. Paradoxically, evidence reveals that ROS are produced more in hypoxic than normoxic cells and serve as signaling molecules that render cells adaptive to hypoxia. As a result, hypoxic tumor cells heavily rely on antioxidant systems to sustain the ROS homeostasis. Thereby, they become sensitive to insults that impair the ROS detoxification network, which has been verified in diverse models with or without radiation. Of note, hypoxic radioresistance has been overviewed in different contexts. To the best of our knowledge, this review is the first to systemically summarize the interplay among radiation, hypoxia, and ROS, and to discuss whether perturbation of ROS homeostasis could provide a new avenue to tackle hypoxic radioresistance.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11010112