To demonstrate how a GMM approach could be exploited for multiclass classification using data from a candidate marker, we analyzed the insulin-like growth factor I receptor (IGF1R), a promising target, but a marker of uncertain importance in breast cancer.
The insulin-like growth factor (IGF) pathway plays a role in breast involution, and systemic changes in this developmental pathway occur with hypertensive disorders of pregnancy (HDP), which have also been associated with lower breast cancer risk, especially in women carrying a functional variant of IGF1R SNP rs2016347.
We studied the effect of insulin-like growth factor one receptor (IGF1R) inhibition in aromatase inhibitor-resistant breast cancer cell lines and fulvestrant-resistant cell lines which were uniquely established in our laboratory.
In addition, we found using Bayesian network-based machine learning that 30 NRF1 motif-enriched genes including growth factor receptors-FGFR1, IGF1R; E2Fs transcription factor family-E2F1, E2F3; MAPK pathway-SHC2, GRB2, MAPK1; PI3K-AKT-mTOR signaling pathway-PIK3CD, PIK3R1, PIK3R3, RPS6KB2; WNT signaling pathway-WNT7B, DLV1, DLV2, GSK3B, NRF1, and DDB2, known for its role in DNA repair and involvement in early events associated with metastatic progression of breast cancer cells, were associated with HER2-amplified breast cancer.
HER2 amplified GOC differs from breast cancer due to inherent differences in the HER2 amino-truncation and mutation rate, loss of HER2 expression, alterations in HER2 signalling pathways and differences in insulin-like growth factor-1 receptor and MET expression.
The insulin receptor (INSR) and the insulin growth factor 1 receptor (IGF1R) play important roles in the etiology of both diabetes mellitus and breast cancer.
Our findings suggest that, when expressed and activated in mammary epithelial cells, HybR acts in a manner similar to IGF1R and support further investigation of the role of HybR in breast cancer.
These data suggest that aberrantly upregulated IGF1R in breast cancer cells can be precisely targeted by cis transcription competition, thus providing a useful strategy to target disease genes in the development of novel precision medicine therapies.
Antiestrogen resistance in estrogen receptor positive (ER<sup>+</sup>) breast cancer is associated with increased expression and activity of insulin-like growth factor 1 receptor (IGF1R).
IGF1R pathway inhibitors were effective in inhibiting growth in ER+ ILC cell lines and synergized with endocrine therapy and similarly IGF1R/InsR inhibition reduced proliferation in ILC tumor explant culture.<b>Conclusions:</b> We provide evidence that loss of E-cadherin hyperactivates the IGF1R pathway and increases sensitivity to IGF1R/InsR targeted therapy, thus identifying the IGF1R pathway as a potential novel target in E-cadherin-deficient breast cancers.<i></i>.
This failure of the IGF1R inhibitors was pronounced in breast cancer; multiple trials testing IGF1R inhibition in estrogen receptor-positive breast cancer were conducted, none showed benefit.
It is not fully clarified whether insulin glargine, an analogue with a high affinity for insulin-like growth factor-1 receptor (IGF-1R), increases the risk for cancers that abundantly express IGF-1R such as breast cancer or some types of breast cancer.
The present study aimed to identify the factors associated with the levels of phosphorylated (p)-IGF-1R in breast cancer, their impact on the outcomes of breast cancer patients, and the prognostic value of alterations of p-IGF-1R during neoadjuvant chemotherapy (NAC).
Combining ER and IGF1R targeting with HER2 targeted therapies may be an alternative to HER2 targeted therapy and chemotherapy for patients with HER2/ER/IGF1R positive breast cancer.
In this chapter, we will briefly introduce inhibitors and monoclonal antibodies that target the main growth factor-modulated scenarios including epidermal growth factor receptor (EGFR), transforming growth factor beta (TGF-β), insulin-like growth factor 1 receptor (IGF1R), and fibroblast growth factor receptor (FGFR) signaling pathways in breast cancer therapy.
Clinical trials examining insulin-like growth factor-I receptor (IGF1R)-targeting strategies have emphasized that better predictive biomarkers are required to improve patient selection.Immunohistochemical tumor-specific protein expression of IGF1R, insulin receptor (InsR), and phosphorylated IGF1R/InsR (pIGF1R/InsR) individually and combined in relation to breast cancer prognosis was evaluated in a population-based cohort of 1,026 primary invasive breast cancer patients without preoperative treatment diagnosed in Sweden.
The prognostic (overall survival, OS) and therapeutic (anti-endocrine therapy) co-contribution of IGF1R and SphK1 were investigated using breast cancer patient samples (n = 236) for immunohistochemistry to measure total and phosphorylated IGF1R and SphK1.
IGF1R Protein Expression Is Not Associated with Differential Benefit to Concurrent Trastuzumab in Early-Stage HER2<sup>+</sup> Breast Cancer from the North Central Cancer Treatment Group (Alliance) Adjuvant Trastuzumab Trial N9831.