Diversity of insulin and IGF signaling in breast cancer: Implications for therapy.
Diversity of insulin and IGF signaling in breast cancer: Implications for therapy.
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DOI：
10.1016/j.mce.2021.111213
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发表时间：
2021-05-01
影响因子：
4.1
通讯作者：
Shaw LM
中科院分区：
文献类型：
--
作者：
Lero MW;Shaw LM
本综述强调了胰岛素受体 (IR) 和胰岛素样生长因子 1 受体 (IGF-1R) 信号通路在癌症中的重要性，并评估了其作为治疗靶点的潜力。我们的重点是乳腺癌，但这条途径是许多癌症行为的核心。了解 IR/IGF-1R 信号传导如何影响正常乳腺的功能，为了解其在乳腺癌中的畸变奠定了基础。具体而言，配体（胰岛素、IGF-1 和 IGF-2）、受体及其下游信号传导效应子的表达和功能失调可驱动乳腺癌的发生和进展，通常以亚型依赖性方式。针对这一途径治疗癌症的努力受到多种因素的阻碍，包括缺乏生物标志物来选择对靶向治疗有反应的患者以及对正常代谢的不利影响。为此，我们讨论了旨在克服这些障碍的持续努力。
This review highlights the significance of the insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathway in cancer and assesses its potential as a therapeutic target. Our emphasis is on breast cancer, but this pathway is central to the behavior of many cancers. An understanding of how IR/IGF-1R signaling contributes to the function of the normal mammary gland provides a foundation for understanding its aberrations in breast cancer. Specifically, dysregulation of the expression and function of ligands (insulin, IGF-1 and IGF-2), receptors and their downstream signaling effectors drive breast cancer initiation and progression, often in a subtype-dependent manner. Efforts to target this pathway for the treatment of cancer have been hindered by several factors including a lack of biomarkers to select patients that could respond to targeted therapy and adverse effects on normal metabolism. To this end, we discuss ongoing efforts aimed at overcoming such obstacles.