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DisABLing kidney cancers caused by fumarate hydratase mutations
1Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Cancer Cell
|December 10, 2014
Summary
Kidney cancers with fumarate hydratase loss are vulnerable to treatments targeting reactive oxygen species. This metabolic vulnerability in cancer offers new therapeutic strategies for kidney cancer patients.
Area of Science:
- Oncology
- Cancer Metabolism
- Biochemistry
Background:
- Oncogenic mutations reprogram cellular metabolism, potentially creating therapeutic vulnerabilities.
- Fumarate hydratase (FH) is a key enzyme in the Krebs cycle; its loss is linked to specific cancer types.
Purpose of the Study:
- To investigate the metabolic vulnerabilities associated with fumarate hydratase deficiency in kidney cancer.
- To identify potential therapeutic strategies targeting these vulnerabilities.
Main Methods:
- Analysis of cellular metabolism in kidney cancer models lacking fumarate hydratase.
- Assessment of sensitivity to agents targeting reactive oxygen species (ROS) management.
Main Results:
- Kidney cancers lacking fumarate hydratase exhibit altered cellular metabolism.
- These cancers show increased sensitivity to agents that disrupt reactive oxygen species homeostasis.
Conclusions:
- Loss of fumarate hydratase creates specific metabolic vulnerabilities in kidney cancer.
- Targeting reactive oxygen species pathways represents a promising therapeutic approach for fumarate hydratase-deficient kidney cancers.
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