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Redox Debt Leads to Metabolic Bankruptcy in Tumors
Evan Quon1, Madeleine L Hart1, Lucas B Sullivan1
1Human Biology & Basic Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Trends in Cancer
|April 30, 2020
Abstract:
Lactate dehydrogenase (LDH) accounts for the fermentative component of aerobic glycolysis, a near ubiquitous metabolic alteration in cancer. Recently, Oshima et al. developed a bioavailable LDH inhibitor that decreases tumor growth in mice and functions synergistically with mitochondrial respiration inhibitors. These findings suggest a cooperative mechanism of action that targets redox homeostasis.
Insights
A new lactate dehydrogenase (LDH) inhibitor reduces tumor growth in mice. This inhibitor works with other drugs by targeting cancer
Area of Science:
- Biochemistry
- Cancer Metabolism
- Drug Development
Background:
- Aerobic glycolysis is a common metabolic change in cancer.
- Lactate dehydrogenase (LDH) drives the fermentative aspect of this process.
- Targeting cancer metabolism is a key area of research.
Purpose of the Study:
- To evaluate a novel bioavailable lactate dehydrogenase (LDH) inhibitor.
- To investigate the synergistic effects of this LDH inhibitor with mitochondrial respiration inhibitors.
- To explore the mechanism of action targeting redox homeostasis in cancer.
Main Methods:
- Development of a bioavailable LDH inhibitor.
- In vivo studies in mice to assess tumor growth.
- Combination therapy studies with mitochondrial respiration inhibitors.
Main Results:
- The developed LDH inhibitor demonstrated a decrease in tumor growth in mice.
- The LDH inhibitor exhibited synergistic effects when combined with mitochondrial respiration inhibitors.
- The findings suggest a cooperative mechanism targeting cellular redox balance.
Conclusions:
- Novel LDH inhibitors show promise in reducing tumor growth.
- Combination therapies targeting LDH and mitochondrial respiration may offer enhanced anti-cancer effects.
- Targeting redox homeostasis is a viable strategy in cancer treatment.
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