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MLN4924 Inhibits Renal Cancer via Nuclear FBP1
- Researchers have discovered that MLN4924, a small-molecule inhibitor, can effectively inhibit clear cell renal cell carcinoma (ccRCC) by stabilizing nuclear fructose-1,6-bisphosphatase 1 (FBP1) in tumor cells.
- The study sheds light on the metabolic reprogramming within ccRCC tumors and how MLN4924 disrupts these processes by stabilizing FBP1, a crucial enzyme involved in gluconeogenesis and metabolic regulation, leading to tumor growth inhibition.
- The research highlights the therapeutic potential of targeting nuclear metabolic enzymes to impede cancer progression and exploit tumor metabolism as a treatment avenue.
- MLN4924, also known as pevonedistat, acts as an inhibitor of the NEDD8-activating enzyme (NAE), disrupting the neddylation process and modulating cancer-relevant cellular pathways by stabilizing proteins targeted for degradation.
- Stabilization of nuclear FBP1 by MLN4924 significantly decreases aerobic glycolysis in ccRCC cells, leading to reduced glucose uptake, lactate production, inhibited tumor growth, and increased apoptosis.
- The study emphasizes FBP1's nuclear role in metabolic regulation and its impact on ccRCC progression, suggesting novel therapeutic avenues for cancer treatment targeting metabolic enzymes.
- MLN4924's ability to suppress tumor metabolism through FBP1 stabilization presents a dual-function therapeutic approach disrupting protein turnover mechanisms and reprogramming cancer metabolism in ccRCC.
- Preclinical models demonstrate that MLN4924 administration reduces tumor burden without significant toxicity, indicating the potential for clinical evaluation in ccRCC patients and in combination with existing therapies.
- The study underscores the importance of multi-omics approaches in unraveling cancer complexity and guiding precision medicine, while also highlighting the need for further research on resistance mechanisms and regulatory aspects of FBP1.
- Overall, the findings provide a promising outlook for utilizing MLN4924 and targeting nuclear metabolic enzymes as a novel strategy to counteract tumor metabolism and advance cancer therapies with enhanced clinical efficacy.
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