Polyamines and cancer: implications for chemotherapy and chemoprevention.
Polyamines and cancer: implications for chemotherapy and chemoprevention.
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DOI：
10.1017/erm.2013.3
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发表时间：
2013-02-22
影响因子：
6.2
通讯作者：
Casero RA Jr
中科院分区：
文献类型：
--
作者：
Nowotarski SL;Woster PM;Casero RA Jr
多胺是一种小分子有机阳离子，对真核生物的正常生长和发育至关重要。在正常生理条件下，细胞内多胺浓度通过生物合成和分解代谢酶的动态网络和特征不佳的运输系统进行严格调节。这种精确的调节确保了多胺的细胞内浓度保持在严格控制的限度内。经常观察到肿瘤中多胺的代谢和对多胺的需求经常失调。多胺水平的升高与乳腺癌、结肠癌、肺癌、前列腺癌和皮肤癌有关，并且已经观察到生物合成和催化剂中限速酶的水平改变。基于这些观察结果和肿瘤生长对多胺的绝对需求，多胺途径是化学预防和化学治疗的合理靶点。在这里，我们描述了多胺领域取得的最新进展，并通过讨论多胺通路的动物模型，针对多胺通路的化疗策略，针对多胺通路特异性药物的化疗临床试验，以及正在进行的针对多胺生物合成的临床试验，重点关注多胺和多胺代谢在肿瘤形成中的作用。
Polyamines are small organic cations that are essential for normal cell growth and development in eukaryotes. Under normal physiological conditions, intracellular polyamine concentrations are tightly regulated through a dynamic network of biosynthetic and catabolic enzymes and a poorly characterized transport system. This precise regulation ensures that the intracellular concentration of polyamines is maintained within strictly controlled limits. It has frequently been observed that the metabolism of, and the requirement for, polyamines in tumours is frequently dysregulated. Elevated levels of polyamines have been associated with breast, colon, lung, prostate, and skin cancers, and altered levels of the rate limiting enzymes in both biosynthesis and catabolism have been observed. Based on these observations and the absolute requirement for polyamines in tumour growth, the polyamine pathway is a rational target for chemoprevention and chemotherapeutics. Here we describe the recent advances made in the polyamine field and focus on the roles of polyamines and polyamine metabolism in neoplasia through a discussion of the current animal models for the polyamine pathway, chemotherapeutic strategies that target the polyamine pathway, chemotherapeutic clinical trials for polyamine pathway specific drugs, and ongoing clinical trials targeting polyamine biosynthesis.
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影响因子：
4.9
作者：
Barker, Robert H., Jr.;Liu, Hanlan;Sybertz, Edmund
通讯作者：
Sybertz, Edmund
影响因子：
4.7
作者：
Coleman, CS;Pegg, AE;O'Brien, TG
通讯作者：
O'Brien, TG
影响因子：
3.9
作者：
Babbar, N.;Murray-Stewart, T.;Casero, R. A., Jr.
通讯作者：
Casero, R. A., Jr.
影响因子：
4.1
作者：
BYERS, TL;WIEST, L;PEGG, AE
通讯作者：
PEGG, AE
DOI：
10.1073/pnas.90.16.7804
发表时间：
1993-08-15
影响因子：
11.1
作者：
BELLOFERNANDEZ, C;PACKHAM, G;CLEVELAND, JL
通讯作者：
CLEVELAND, JL