Metformin in breast cancer - an evolving mystery.
Metformin in breast cancer - an evolving mystery.
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乳腺癌中的二甲双胍 - 一个不断发展的谜团。
DOI：
10.1186/s13058-015-0598-8
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发表时间：
2015-06-26
期刊：
影响因子：
--
通讯作者：
Jiralerspong S
中科院分区：
文献类型：
--
作者：
Camacho L;Dasgupta A;Jiralerspong S
二甲双胍是一种具有良好副作用和安全性的糖尿病药物，已被广泛研究其在许多癌症（包括乳腺癌）中的抗肿瘤活性。但它在临床竞技场的作用机制仍然是难以捉摸的。在非糖尿病乳腺癌患者中进行的二甲双胍机会窗口试验中，Dowling和同事检查了该药物对癌细胞的直接作用（由AMP激酶介导）以及其间接作用（由循环胰岛素介导））。数据表明，在这种情况下短期给予二甲双胍具有显著涉及间接胰岛素依赖性途径的抗肿瘤作用。直接途径的作用仍有待确定。这项研究代表了在建立二甲双胍的几种可能机制之一方面向前迈出的重要一步，这些信息将有助于确定二甲双胍大型临床试验中评估的候选生物标志物，例如正在进行的NCIC CTG MA. 32辅助二甲双胍试验。本文讨论了这些数据对二甲双胍治疗乳腺癌的潜在意义。
Metformin, a diabetes drug with well-established side effect and safety profiles, has been widely studied for its anti-tumor activities in a number of cancers, including breast cancer. But its mechanism of action in the clinical arena remains elusive. In a window of opportunity trial of metformin in non-diabetic breast cancer patients, Dowling and colleagues examined both the direct actions of the drug on cancer cells (as mediated by AMP kinase), as well as its indirect actions (as mediated by circulating insulin). The data suggest that short-term administration of metformin in this setting has anti-tumor effects significantly involving the indirect, insulin-dependent pathway. The role of the direct pathway remains to be determined. This study represents an important step forward in establishing one of several possible mechanisms for metformin, information that will be useful in determining candidate biomarkers to evaluate in large clinical trials of metformin, such as the ongoing NCIC CTG MA.32 trial of adjuvant metformin. The potential significance of these data for metformin in the treatment of breast cancer is discussed here.
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