Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer.
Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer.
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DOI：
10.1038/sj.bjc.6604554
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发表时间：
2008-10-07
影响因子：
8.8
通讯作者：
Mackey, J. R.
中科院分区：
文献类型：
--
作者：
Michelakis, E. D.;Webster, L.;Mackey, J. R.
大多数实体瘤的独特代谢（有氧糖酵解，即，瓦尔堡效应）不仅是代谢成像诊断癌症的基础，而且还可能与作为癌症特征的细胞凋亡抗性有关。癌症中的糖酵解表型似乎是癌症中不同分子异常的共同点，并且可能与线粒体功能的（潜在可逆的）抑制相关。仿制药二氯乙酸是一种口服小分子，通过抑制丙酮酸脱氢酶激酶，增加丙酮酸进入线粒体的流量，促进葡萄糖氧化而不是糖酵解。这逆转了癌症中受抑制的线粒体凋亡，并导致体外和体内肿瘤生长的抑制。在这里，我们回顾了支持这种有前途的代谢调节剂在早期癌症临床试验中快速翻译的科学和临床原理。
The unique metabolism of most solid tumours (aerobic glycolysis, i.e., Warburg effect) is not only the basis of diagnosing cancer with metabolic imaging but might also be associated with the resistance to apoptosis that characterises cancer. The glycolytic phenotype in cancer appears to be the common denominator of diverse molecular abnormalities in cancer and may be associated with a (potentially reversible) suppression of mitochondrial function. The generic drug dichloroacetate is an orally available small molecule that, by inhibiting the pyruvate dehydrogenase kinase, increases the flux of pyruvate into the mitochondria, promoting glucose oxidation over glycolysis. This reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Here, we review the scientific and clinical rationale supporting the rapid translation of this promising metabolic modulator in early-phase cancer clinical trials.
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DOI：
10.1073/pnas.0611662104
发表时间：
2007-05-29
影响因子：
11.1
作者：
Cairns, Rob A.;Papandreou, Ioanna;Denko, Nicholas C.
通讯作者：
Denko, Nicholas C.
影响因子：
8
作者：
Stacpoole, PW;Kerr, DS;Valenstein, E
通讯作者：
Valenstein, E
影响因子：
11.2
作者：
Pastorino, JG;Hoek, JB;Shulga, N
通讯作者：
Shulga, N
影响因子：
2.8
作者：
Cao, Wengang;Yacoub, Saif;Rosser, Charles J.
通讯作者：
Rosser, Charles J.
影响因子：
10.5
作者：
Gottlob, K;Majewski, N;Hay, N
通讯作者：
Hay, N