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

• Published in: Molecular and cellular endocrinology Vol. 527; p. 111213
• Main Authors: Lero, Michael W., Shaw, Leslie M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.05.2021
• Subjects: Antigens, CD - genetics; Antigens, CD - metabolism; biomarkers; Breast cancer; breast neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Female; Humans; IGF-1R; Insulin; Insulin receptor; insulin receptors; Insulin-like growth factor (IGF); Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; insulin-like growth factor I receptor; Insulin-Like Growth Factor II - genetics; Insulin-Like Growth Factor II - metabolism; ligands; mammary glands; metabolism; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Receptor, IGF Type 1 - genetics; Receptor, IGF Type 1 - metabolism; Receptor, Insulin - genetics; Receptor, Insulin - metabolism; Signal Transduction; therapeutics; Therapy; Signal transduction; Therapy; Breast cancer; Insulin receptor; IGF-1R; Insulin; Insulin-like growth factor (IGF)
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/j.mce.2021.111213

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.