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. Author manuscript; available in PMC: 2022 May 1.
Published in final edited form as: Mol Cell Endocrinol. 2021 Feb 17;527:111213. doi: 10.1016/j.mce.2021.111213

Figure 2: Functional outcomes of the IR/IGF-1R/IRS pathway in normal and breast cancer settings.

Figure 2:

Ligands are expressed both systemically (from the liver and pancreas) and locally in the breast in both normal and cancer and elevated ligand expression is observed in breast cancer. In normal tissues (on left), stimulation of the IR-B and IGF-1R regulates glucose homeostasis and growth, respectively. In breast cancer (on right), expression of IR-A and IGF-1R is increased. Systemic factors such as obesity and type 2 diabetes (T2D) promote pathway activity by upregulating ligand and receptor expression. Moreover, hypoxic tumor microenvironments enhance IRS-2 expression. The IR/IGF-1R pathway cross-talks with the estrogen receptor (ER) pathway to enhance signaling and promote tumor growth and progression. Targeted inhibitors are shown that disrupt pathway function (white boxes): FMD, fasting mimicking diet; IGFi, inhibitory IGF-1 and IGF-2 antibodies; IGF-1Ri, inhibitory IGF-1R antibodies; RTKi, IR/IGF-1R tyrosine kinase inhibitors; PI3Ki, PI3K inhibitors; SERM, selective estrogen receptor modulators; SERD, selective estrogen receptor degraders. T2D, Type 2 Diabetes; SHBG, sex-hormone binding globulin; IGFBP, insulin-like growth factor binding protein