Inhibition of glutaminolysis in combination with other therapies to improve cancer treatment.

Inhibition of glutaminolysis in combination with other therapies to improve cancer treatment.
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抑制谷氨酰胺分解与其他疗法相结合,以改善癌症治疗。

DOI:
10.1016/j.cbpa.2021.01.006
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发表时间:
2021-06
影响因子:
7.8
通讯作者:
Le A
Le A
中科院分区:
生物学2区
文献类型:
--
作者:
Shen YA;Chen CL;Huang YH;Evans EE;Cheng CC;Chuang YJ;Zhang C;Le A

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以谷氨酰胺为靶点的肿瘤治疗方法越来越受到人们的关注。催化酶如谷氨酰胺分解中的谷氨酰胺酶(GLS),谷氨酰胺转化为谷氨酸,然后转化为α-酮戊二酸(三羧酸(TCA)循环的中间体)的一系列生化反应,可以被小分子抑制剂靶向,其中一些正在进行早期临床试验,并显示出有希望的安全性。然而,已经观察到对氨解靶向治疗的抗性,需要开发治疗来对抗这种抗性。一种选择是使用协同药物组合,这可以提高肿瘤化疗的有效性,减少耐药性和副作用。本综述将重点介绍涉及β-内酰胺酶途径的研究和具有治疗意义的多种联合疗法。
Targeting glutamine catabolism has been attracting more research attention on the development of successful cancer therapy. Catalytic enzymes such as glutaminase (GLS) in glutaminolysis, a series of biochemical reactions by which glutamine is converted to glutamate and then alpha-ketoglutarate, an intermediate of the tricarboxylic acid (TCA) cycle, can be targeted by small molecule inhibitors, some of which are undergoing early phase clinical trials and exhibiting promising safety profiles. However, resistance to glutaminolysis targeting treatments has been observed, necessitating the development of treatments to combat this resistance. One option is to use synergy drug combinations, which improve tumor chemotherapy’s effectiveness and diminish drug resistance and side effects. This review will focus on studies involving the glutaminolysis pathway and diverse combination therapies with therapeutic implications.
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