Redox Paradox: A Novel Approach to Therapeutics-Resistant Cancer

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66 Scopus citations

Abstract

Significance: Cancer cells that are resistant to radiation and chemotherapy are a major problem limiting the success of cancer therapy. Aggressive cancer cells depend on elevated intracellular levels of reactive oxygen species (ROS) to proliferate, self-renew, and metastasize. As a result, these aggressive cancers maintain high basal levels of ROS compared with normal cells. The prominence of the redox state in cancer cells led us to consider whether increasing the redox state to the condition of oxidative stress could be used as a successful adjuvant therapy for aggressive cancers. Recent Advances: Past attempts using antioxidant compounds to inhibit ROS levels in cancers as redox-based therapy have met with very limited success. However, recent clinical trials using pro-oxidant compounds reveal noteworthy results, which could have a significant impact on the development of strategies for redox-based therapies. Critical Issues: The major objective of this review is to discuss the role of the redox state in aggressive cancers and how to utilize the shift in redox state to improve cancer therapy. We also discuss the paradox of redox state parameters; that is, hydrogen peroxide (H2O2) as the driver molecule for cancer progression as well as a target for cancer treatment. Future directions: Based on the biological significance of the redox state, we postulate that this system could potentially be used to create a new avenue for targeted therapy, including the potential to incorporate personalized redox therapy for cancer treatment.

Original languageEnglish
Pages (from-to)1237-1272
Number of pages36
JournalAntioxidants and Redox Signaling
Volume29
Issue number13
DOIs
StatePublished - Nov 1 2018

Bibliographical note

Funding Information:
This work was supported in part by NIH grants CA188792, CA205400-02, and NIH/NIGMS COBRE program (P20 GM121327). The authors would like to thank Dr. Heidi Weiss, Dana Napier, and Rani Jayswal for technical assistance and statistical analysis of data in Figure 3. This research utilized the service facilities of the Markey Biospecimen Procurement and Translational Pathology Shared Resource Facility as well as the Biostatistics and Bioinformatics Shared Resource Facility, and it was funded by a Markey Cancer Center support grant (P30 CA177558).

Publisher Copyright:
© 2018, Mary Ann Liebert, Inc., publishers.

Keywords

  • HO
  • Redox state
  • personalized redox therapy
  • resistant cancer
  • rewired redox state

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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