Journal
KIDNEY CANCER
Volume 3, Issue 1, Pages 15-29Publisher
IOS PRESS
DOI: 10.3233/KCA-180043
Keywords
Kidney cancer; renal cell carcinoma; treatment; glutamine; metabolism; metabolic reprogramming; glutaminase; glutaminase inhibitor; biomarkers
Categories
Funding
- Conquer Cancer Foundation
- NIH/NCI [5U54CA199075]
- Calithera Biosciences, Inc.
- NIH/NCI
- Stanford University Translational Research and Applied Medicine (TRAM) award
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An important hallmark of cancer is 'metabolic reprogramming' or the rewiring of cellular metabolism to support rapid cell proliferation [1-5]. Metabolic reprogramming through oncometabolite-mediated transformation or activation of oncogenes in renal cell carcinoma (RCC) globally impacts energy production as well as glucose and glutamine utilization in RCCcells, which can promote dependence on glutamine supply to support cell growth and proliferation [6, 7]. Novel inhibitors of glutaminase, a key enzyme in glutamine metabolism, target glutamine addiction as a viable treatment strategy in metastatic RCC (mRCC). Here, we review glutamine metabolic pathways and how changes in cellular glutamine utilization enable the progression of RCC. This overview provides scientific rationale for targeting this pathway in patients with mRCC. We will summarize the current understanding of cellular and molecular mechanisms underlying anti-tumor efficacy of glutaminase inhibitors in RCC, provide an overview of clinical efforts targeting glutaminase in mRCC, and review approaches for identifying biomarkers for patient stratification and detecting therapeutic response early on in patients treated with this novel class of anti-cancer drug. Ultimately, results of ongoing clinical trials will demonstrate whether glutaminase inhibition can be a worthy addition to the current armamentarium of drugs used for patients with mRCC.
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