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Metabolic Pathways in Kidney Cancer: Current Therapies and Future Directions
W Kimryn Rathmell1, Jeffrey C Rathmell1, W Marston Linehan1
1W. Kimryn Rathmell and Jeffrey C. Rathmell, Vanderbilt-Ingram Cancer Center and Vanderbilt University Medical Center, Nashville, TN; W. Marston Linehan, National Institutes of Health, Bethesda, MD.
Background:
Renal cell carcinoma (RCC) has become known as a metabolic disease, owing to the diverse array of metabolic defects and perturbations that occur as a result of the unique genetics that can drive these tumors. Recent attention to this feature of RCCs has fueled interest in targeting metabolism as a therapeutic strategy.
Methods:
We conducted a literature search to develop themes around discrete pathways or processes of cellular metabolism, provide a framework for understanding emerging therapeutic strategies, and consider future interventions.
Results:
Defects occur in metabolic pathways ranging from glycolysis to mitochondrial function and affect not only the tumor cell functionality, but also the local environment. We identified opportunities for therapeutic intervention associated with each pathway.
Conclusion:
The metabolism of RCC cells presents a special environment of tumor susceptibilities, with opportunities for novel imaging applications and treatment paradigms that are being tested in monotherapy or as adjuncts to targeted or immune-based strategies.
Insights
Renal cell carcinoma (RCC) is a metabolic disease driven by genetic mutations. Targeting cancer metabolism offers new therapeutic strategies for RCC, including novel imaging and treatment approaches.
Area of Science:
- Oncology
- Cancer Metabolism
- Renal Cell Carcinoma
Background:
- Renal cell carcinoma (RCC) exhibits metabolic disease characteristics due to genetic drivers.
- Metabolic defects are increasingly recognized as key features of RCC tumorigenesis.
Purpose of the Study:
- To review cellular metabolism pathways in RCC.
- To establish a framework for understanding emerging therapeutic strategies targeting cancer metabolism.
- To identify future intervention opportunities.
Main Methods:
- Literature search on cellular metabolism in RCC.
- Thematic analysis of metabolic pathways and therapeutic targets.
- Identification of intervention points within metabolic processes.
Main Results:
- Metabolic defects identified across pathways including glycolysis and mitochondrial function.
- Dysregulated metabolism impacts tumor cell function and the tumor microenvironment.
- Specific opportunities for therapeutic intervention were linked to identified metabolic pathways.
Conclusions:
- RCC cellular metabolism creates unique tumor vulnerabilities.
- Opportunities exist for novel imaging applications in RCC.
- New treatment paradigms, including monotherapy and combination strategies, are emerging.
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