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Clinically Evaluated Cancer Drugs Inhibiting Redox Signaling
D Lynn Kirkpatrick1, Garth Powis2
11 PHusis Therapeutics, Inc., La Jolla, California.
Significance:
There are a number of redox-active anticancer agents currently in development based on the premise that altered redox homeostasis is necessary for cancer cell's survival. Recent Advances: This review focuses on the relatively few agents that target cellular redox homeostasis to have entered clinical trial as anticancer drugs.
Critical Issues:
The success rate of redox anticancer drugs has been disappointing compared to other classes of anticancer agents. This is due, in part, to our incomplete understanding of the functions of the redox targets in normal and cancer tissues, leading to off-target toxicities and low therapeutic indexes of the drugs. The field also lags behind in the use biomarkers and other means to select patients who are most likely to respond to redox-targeted therapy.
Future Directions:
If we wish to derive clinical benefit from agents that attack redox targets, then the future will require a more sophisticated understanding of the role of redox targets in cancer and the increased application of personalized medicine principles for their use. Antioxid. Redox Signal. 26, 262-273.
Insights
Redox-active anticancer drugs targeting cellular redox homeostasis show promise but face challenges. Future success requires a deeper understanding of redox targets and personalized medicine approaches for cancer treatment.
Area of Science:
- Oncology
- Biochemistry
- Pharmacology
Background:
- Altered cellular redox homeostasis is a key factor in cancer cell survival.
- Redox-active anticancer agents are under development to target this vulnerability.
Purpose of the Study:
- To review redox-active agents that have advanced to clinical trials for cancer treatment.
- To analyze the challenges and future directions for this class of anticancer drugs.
Main Methods:
- Literature review of redox-active anticancer agents in clinical development.
- Analysis of factors contributing to the success and limitations of these agents.
Main Results:
- Few redox-targeting agents have reached clinical trials.
- Disappointing success rates are attributed to incomplete understanding of redox targets and off-target toxicities.
- Limited use of biomarkers for patient selection hinders therapeutic efficacy.
Conclusions:
- Further clinical benefit from redox-targeting agents necessitates a sophisticated understanding of redox roles in cancer.
- Personalized medicine principles are crucial for optimizing the use of these drugs.
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