The IGF Hormonal Network in Endometrial Cancer: Functions, Regulation, and Targeting Approaches.

The IGF Hormonal Network in Endometrial Cancer: Functions, Regulation, and Targeting Approaches.
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DOI:
10.3389/fendo.2014.00076
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发表时间:
2014
影响因子:
5.2
通讯作者:
Werner H
Werner H
中科院分区:
医学2区
文献类型:
--
作者:
Bruchim I;Sarfstein R;Werner H

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流行病学以及临床和实验数据表明,胰岛素样生长因子(IGF1、IGF2)在妇科癌症(尤其是子宫内膜肿瘤)中发挥着重要作用。 IGF1 受体 (IGF1R) 介导两种配体的增殖和抗凋亡活性,近年来成为肿瘤学中有前途的治疗靶点。然而,迄今为止进行的大多数临床试验都得出了不同的结果,强调需要确定可以预测抗 IGF1R 靶向治疗反应的生物标志物。本文将回顾有关 IGF 系统成分在子宫内膜癌中的作用和表达的最新数据。此外,我们将回顾有关 IGF 信号通路与肿瘤抑制因子 p53 和乳腺癌易感基因 1 (BRCA1) 之间相互作用的数据。抗癌基因 p53 和 BRCA1 在妇科癌症的病因学中发挥着关键作用,因此,它们与 IGF1R 的相互作用在转化方面具有高度相关性。更好地了解 IGF 系统调节的复杂机制将提高我们开发子宫内膜肿瘤有效治疗方式的能力。
Epidemiological as well as clinical and experimental data identified the insulin-like growth factors (IGF1, IGF2) as important players in gynecological cancers in general, and endometrial tumors in particular. The IGF1 receptor (IGF1R), which mediates the proliferative and anti-apoptotic activities of both ligands, emerged in recent years as a promising therapeutic target in oncology. However, most clinical trials conducted so far led to mixed results, emphasizing the need to identify biomarkers that can predict responsiveness to anti-IGF1R-targeted therapies. This article will review recent data regarding the role and expression of IGF system components in endometrial cancer. In addition, we will review data on the interplay between the IGF signaling pathway and tumor suppressors p53 and breast cancer susceptibility gene-1 (BRCA1). Anti-oncogenes p53 and BRCA1 play a key role in the etiology of gynecological cancers and, therefore, their interaction with IGF1R is of high relevance in translational terms. A better understanding of the complex mechanisms underlying the regulation of the IGF system will improve our ability to develop effective treatment modalities for endometrial tumors.
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