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透明细胞肾细胞癌的代谢重编程。

Metabolic reprogramming of clear cell renal cell carcinoma.

机构信息

Department of Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Front Endocrinol (Lausanne). 2023 Jun 6;14:1195500. doi: 10.3389/fendo.2023.1195500. eCollection 2023.

Abstract

Clear cell renal cell carcinoma (ccRCC) is a malignancy that exhibits metabolic reprogramming as a result of genetic mutations. This reprogramming accommodates the energy and anabolic needs of the cancer cells, leading to changes in glucose, lipid, and bio-oxidative metabolism, and in some cases, the amino acid metabolism. Recent evidence suggests that ccRCC may be classified as a metabolic disease. The metabolic alterations provide potential targets for novel therapeutic interventions or biomarkers for monitoring tumor growth and prognosis. This literature review summarized recent discoveries of metabolic alterations in ccRCC, including changes in glucose, lipid, and amino acid metabolism. The development of metabolic drugs targeting these metabolic pathways was also discussed, such as HIF-2α inhibitors, fatty acid synthase (FAS) inhibitors, glutaminase (GLS) inhibitors, indoleamine 2,3-dioxygenase (IDO) inhibitors, and arginine depletion. Future trends in drug development are proposed, including the use of combination therapies and personalized medicine approaches. In conclusion, this review provides a comprehensive overview of the metabolic alterations in ccRCC and highlights the potential for developing new treatments for this disease.

摘要

透明细胞肾细胞癌(ccRCC)是一种恶性肿瘤,由于基因突变而表现出代谢重编程。这种重编程适应了癌细胞的能量和合成代谢需求,导致葡萄糖、脂质和生物氧化代谢发生变化,在某些情况下还会导致氨基酸代谢发生变化。最近的证据表明,ccRCC 可能被归类为一种代谢疾病。这些代谢改变为新型治疗干预措施或监测肿瘤生长和预后的生物标志物提供了潜在的靶点。本文综述总结了 ccRCC 中代谢改变的最新发现,包括葡萄糖、脂质和氨基酸代谢的变化。还讨论了针对这些代谢途径的代谢药物的开发,如 HIF-2α 抑制剂、脂肪酸合酶(FAS)抑制剂、谷氨酰胺酶(GLS)抑制剂、吲哚胺 2,3-双加氧酶(IDO)抑制剂和精氨酸耗竭剂。提出了药物开发的未来趋势,包括联合治疗和个性化医疗方法的应用。总之,本文综述全面概述了 ccRCC 的代谢改变,并强调了为这种疾病开发新治疗方法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b0f/10280292/c10f798e0c81/fendo-14-1195500-g001.jpg

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