W Kimryn Rathmell1, Jeffrey C Rathmell1, W Marston Linehan1. 1. W. 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.
Abstract
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.
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.
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