Anticancer agents that counteract tumor glycolysis.
Anticancer agents that counteract tumor glycolysis.
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DOI：
10.1002/cmdc.201200176
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发表时间：
2012-08
期刊：
影响因子：
3.4
通讯作者：
Minutolo, Filippo
中科院分区：
文献类型：
--
作者：
Granchi, Carlotta;Minutolo, Filippo
我们可以把癌症看作是一种“代谢性疾病”吗？肿瘤是代谢选择的结果，形成由异质细胞组成的组织，这些细胞通常表达过度活跃的代谢作为共同特征。事实上，癌细胞必须处理对能量和生物合成中间体的需求增加，以支持其生长和侵袭性。然而，它们的高增殖率经常产生氧合不充分的区域。因此，它们的碳水化合物代谢必须主要依赖于与氧化磷酸化解偶联的糖酵解过程。这种代谢开关，也称为“瓦尔堡效应”，构成了肿瘤细胞对相对不利环境的基本适应，并支持侵袭性和转移性表型的演变。因此，肿瘤糖酵解可能成为癌症治疗的一个有吸引力的靶点。这种方法经常引起人们的担忧，即抗糖酵解剂可能对正常细胞造成严重的副作用。事实上，对癌细胞的选择性作用的关键可以在它们对糖酵解的双曲线成瘾中找到，这可以用来产生毒性最小的新抗癌药物。事实上，越来越多的证据支持许多糖酵解酶和转运蛋白作为癌症治疗的合适候选靶点。在这里，我们回顾了一些最相关的抗糖酵解剂，迄今为止已被调查的癌症治疗。
Can we consider cancer as a “metabolic disease”? Tumors are the result of a metabolic selection, forming tissues composed of heterogeneous cells that generally express an overactive metabolism as a common feature. In fact, cancer cells have to deal with increased needs for both energy and biosynthetic intermediates, in order to support their growth and invasiveness. However, their high proliferation rate often generates regions that are not sufficiently oxygenated. Therefore, their carbohydrate metabolism has to rely mostly on a glycolytic process that is uncoupled from oxidative phosphorylation. This metabolic switch, also known as the “Warburg Effect”, constitutes a fundamental adaptation of the tumor cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumor glycolysis may constitute an attractive target for cancer therapy. This approach has often raised concerns that anti-glycolytic agents may cause serious side effects on normal cells. Actually, the key for a selective action against cancer cells can be found in their hyperbolic addiction to glycolysis, which may be exploited to generate new anti-cancer drugs showing minimal toxicity. In fact, there is growing evidence that supports many glycolytic enzymes and transporters as suitable candidate targets for cancer therapy. Herein we review some of the most relevant anti-glycolytic agents that have been investigated so far for the treatment of cancer.
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影响因子：
2.9
作者：
ANDERSON, VE;WEISS, PM;CLELAND, WW
通讯作者：
CLELAND, WW
影响因子：
7.3
作者：
Aronov, AM;Verlinde, CLMJ;Gelb, MH
通讯作者：
Gelb, MH
影响因子：
9.3
作者：
Ben-Haim, Simona;Ell, Peter
通讯作者：
Ell, Peter
DOI：
10.1073/pnas.052131799
发表时间：
2002-04-30
影响因子：
11.1
作者：
Arsenieva, D;Hardré, R;Jeffery, CJ
通讯作者：
Jeffery, CJ
DOI：
10.1073/pnas.96.8.4273
发表时间：
1999-04-13
影响因子：
11.1
作者：
Aronov, AM;Suresh, S;Gelb, MH
通讯作者：
Gelb, MH