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Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?

Nature reviews. Drug discovery

metabolism, Reactive Oxygen Species, Oxidation-Reduction, Neoplastic Stem Cells, drug therapy, Neoplasms, Humans, Glutathione, Drug Resistance, Neoplasm, Animals, Adaptation, Physiological

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      Abstract

      Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, and recent studies suggest that this biochemical property of cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumours frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially eliminate these cells by pharmacological ROS insults. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. We argue that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.

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      Journal
      10.1038/nrd2803
      19478820

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