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Review
. 2021 Mar 22:9:641449.
doi: 10.3389/fcell.2021.641449. eCollection 2021.

Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer

Anna Ianza  1 , Marianna Sirico  2   3 , Ottavia Bernocchi  1 , Daniele Generali  1   3   4
Affiliations
Review

Role of the IGF-1 Axis in Overcoming Resistance in Breast Cancer

Anna Ianza et al. Front Cell Dev Biol. .

Abstract

Over the last two decades, many studies have demonstrated that the insulin-like growth factor-1 (IGF-1) is involved in a number of patho-physiological processes, as well as in the development of different types of solid tumors, including breast cancer (BC). Preclinical and clinical data showed that IGF-1 receptor (R) is overexpressed and hyper-phosphorylated in several subtypes of BCs. The central implications of this pathway in tumor cell proliferation and metastasis make it an important therapeutic target. Moreover, the IGF-1 axis has shown strong interconnection with estrogen regulation and endocrine therapy, suggesting a possible solution to anti-estrogen resistance. IGF-1R might also interfere with other pivotal therapeutic strategies, such as anti HER2 treatments and mTOR inhibitors; several clinical trials are ongoing evaluating the role of IGF-1R inhibition in modulating resistance mechanisms to target therapies. Our aim is to offer an overview of the most recent and significant field of application of IGF-1 inhibitors and relevant therapeutic strategies, weighing their possible future impact on clinical practice.

Keywords: IGF-1R; IGF1; breast cancer; clinical trial; therapy resistance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
A schematic diagram of insulin growth factor-1 receptor (IGF-IR) activation and regulation. The IGF axis consists of ligands as insulin, insulin-like growth factor 1 and 2 (IGF-1, IGF-2), receptor, IGF binding proteins (IGFBPs) 1–7, and IGFBP proteases. The IGF ligands bind their receptors and binding proteins with high affinity. IGFBPs bind tightly to IGF ligands, influencing binding to their receptors; IGFBP proteases cleave the IGFBPs into fragments with lower affinity for the IGF ligands, thereby increasing free IGF-1 and IGF-2 bioavailability. Activation of IGF-1R promotes cellular growth, proliferation, survival, and metastasis via activation of molecular pathways downstream; among them the phosphatidylinositol 3-kinase (PI3K)-AKT and RAS-extracellular signal-regulated kinase (ERK) pathways.
See this image and copyright information in PMC

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