Concern over growth-promoting activity of insulin glargine turned out to be ill-founded when the circulating moiety after injection was noted to have a lower IGF-1:insulin activity than human insulin, and a direct study of retinopathy progression or meta-analysis of malignancy incidence failed to show signals of concern.
Nevertheless, while IGF-1 levels are associated with increased cancer risk, they have been paradoxically implicated with protection from other age-related conditions, particularly in the brain, suggesting that strategies aimed at selectively increasing central IGF-1 action may have favorable effects on aging.
Introduction Growing evidence indicates that circulating concentrations of insulin-like growth factor 1 (IGF-I), along with IGF-I relative to IGF-binding proteins (IGFBP), are associated with an increased risk of cancer.
We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer.
However, the IGF-1rs35767 A>G polymorphism was significantly associated with increased cancer risk for all genetic models (G vs A: OR = 1.087, 95% CI: 1.036-1.141, Ph = .338; GG vs AA: OR = 1.272, 95% CI: 1.121-1.442, Ph = .359; AG vs AA: OR = 1.187, 95% CI: 1.043-1.351, Ph = .695; AG+GG vs AA: OR = 1.187, 95% CI: 1.043-1.351, Ph = .695; GG vs AA+AG: OR = 1.086, 95% CI: 1.025-1.151, Ph = .275).
To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross-sectional associations of these exposures with circulating concentrations of IGFs (IGF-I and IGF-II) and IGFBPs (IGFBP-1, IGFBP-2 and IGFBP-3).
The present study demonstrated that miR‑939 exerted tumor‑suppressing roles in the malignancy of OS cells by directly targeting IGF‑1R and inactivating the PI3K/AKT pathway.
The aim of the present study was to determine the relative expression, cellular location, and prognostic significance of HER-family members, the EGFR mutant (EGFRvIII) c-MET, IGF-1R and the cancer stem cell biomarker CD44 in 60 patients with FIGO stage III and IV ovarian cancer.
From a clinical point of view, the IR-A overexpression in cancer may be a determinant factor for the resistance to IGF-1R target therapies for this issue.
<b>Purpose:</b> Insulin-like growth factor receptor 1 (IGF-1R) is critically involved in pancreatic cancer pathophysiology, promoting cancer cell survival and therapeutic resistance.
In particular, the mitogenic insulin receptor isoform A (IR-A) and the insulin-like growth factor receptor (IGF-1R) are frequently overexpressed in cancer together with their cognate ligands IGF-1 and IGF-2.
Binding of insulin-like growth factor-I (IGF-1) to its receptor (IGF-1R) initiates downstream signals that activate PI3K/Akt/mTOR and MEK/Erk pathways, which stimulate cancer cell proliferation and induce drug resistance.
We provided evidence of DB as a potential therapeutic agent for overcoming 5-FU resistance induced by IGF1, and suppressing cancer stem-like properties in association with miR-214 regulation.
IGF-1 receptor (IGF-1R) and integrin cooperative signaling promotes cancer cell survival, proliferation, and motility, but whether this influences cancer progression and therapy responses is largely unknown.
Articles regarding the relationship between IGF1rs5742714, rs6214, and rs6220 polymorphisms and cancer risk were selected by searching the PubMed, Embase, and Web of Science databases before April 30, 2018.
Lowering insulin and insulin-like growth factor 1 (IGF-1) levels that stimulate cancer growth could be important features of metformin's mode of action.
Circulating concentrations of IGF-I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre-diagnostic circulating IGF-I concentrations and bladder cancer has never been studied prospectively.