4.5 Article

Diversity of insulin and IGF signaling in breast cancer: Implications for therapy

Journal

MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 527, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2021.111213

Keywords

Insulin; Insulin-like growth factor (IGF); Insulin receptor; IGF-1R; Breast cancer; Signal transduction; Therapy

Funding

  1. NIH [CA240655, CA229910]

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This review underscores the significance of the IR/IGF-1R signaling pathway in cancer and its potential as a therapeutic target. Understanding the pathway's role in normal mammary gland function provides insight into its aberrations in breast cancer. However, efforts to target this pathway for cancer treatment are hindered by a lack of biomarkers and adverse effects on normal metabolism.
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.

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