Activation of the Insulin-like Growth Factor-1 Receptor Induces Resistance to Epidermal Growth Factor Receptor Antagonism in Head and Neck Squamous Carcinoma Cells

Jameson, Mark J.; Beckler, Andrew D.; Taniguchi, Linnea E.; Allak, Amir; VanWagner, Lisa B.; Lee, Nora G.; Thomsen, William; Hubbard, Matthew A.; Thomas, Christopher Y.

doi:10.1158/1535-7163.mct-11-0294

Cited by 75 publications

(89 citation statements)

References 36 publications

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“…Li et al demonstrated that the expression of JUN in fibroblasts in the tumour microenvironment can promote the secretion of IGF-1. They also showed IGF-1 acting as a paracrine molecule that stimulates epithelial cell proliferation [29,30]. IGF-1 receptor (IGF-1R) activation was also found to be able to suppress anoikis and hence to promote the development of metastases [31,32].…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of the tumour-adjacent tissue in head and neck cancers

et al. 2015

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Even with significant advances in operative skills and adjuvant therapies, the overall survival of patients suffering with head and neck squamous cancers (HNSCC) is unsatisfactory. Accordingly, no clinically useful prognostic biomarkers have been found yet for HNSCC. Many studies analysed the expression of potential markers in tumour tissues compared to adjacent tissues. Nevertheless, due to the sharing of the same microenvironment, adjacent tissues show molecular similarity to tumour tissues. Thus, gene expression patterns of 94 HNSCC tumorous tissues were compared with 31 adjacent tissues and with 10 tonsillectomy specimens of non-cancer individuals. The genes analysed at RNA level using quantitative RT-PCR and correlated with clinico-pathological conditions were as follows: EGF, EGFR, MKI67, BCL2, BAX, FOS, JUN, TP53, VEGF, FLT1, MMP2, MMP9, MT1A and MT2A. The elevated MT2A, BAX, EGF and JUN expression was associated with the influence of tumour cells on the rearrangement of healthy tissues, as well as a significant shift in the BAX/BCL2 ratio. Our investigation also indicated that adjacent tissues play an important role in cancerogenesis by releasing several tumour-supporting factors such as EGF. A gradual increase in the metallothionein expression, from the lowest one in tonsillectomy samples to the highest ones in tumour samples, suggests that MT expression might be tissue reaction to the presence of tumour cells. The results of this study confirmed the significance of metallothionein in tumori-genesis and gave evidences for its use as a potential HNSCC biomarker. Furthermore, this study highlighted the importance of histologically normal tumour-adjacent tissue in prediction of HNSCC progress.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of the tumour-adjacent tissue in head and neck cancers

et al. 2015

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“…10 Furthermore, cross-talk between the IGF1R and EGFR receptor has been shown to result in compensation and resistance during targeted inhibition of either receptor. 11 Finally, various preclinical studies have shown improved activity when both IGF1R and EGFR are inhibited concomitantly. 12,13 Given that anti-IGF1R and anti-EGFR antibodies have shown toxicity clinically, it is important to study the combined effects of anti-IGF1R and anti-EGFR treatment quantitatively.…”

Section: Resultsmentioning

confidence: 99%

A New Bliss Independence Model to Analyze Drug Combination Data

Zhao¹,

Sachsenmeier²,

et al. 2014

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The Bliss independence model is widely used to analyze drug combination data when screening for candidate drug combinations. The method compares the observed combination response (Y O ) with the predicted combination response (Y P ), which was obtained based on the assumption that there is no effect from drug-drug interactions. Typically, the combination effect is declared synergistic if Y O is greater than Y P . However, this method lacks statistical rigor because it does not take into account the variability of the response measures and can frequently cause false-positive claims. In this article, we introduce a two-stage response surface model to describe the drug interaction across all dose combinations tested. This new method enables robust statistical testing for synergism at any dose combination, thus reducing the risk of false positives. The use of the method is illustrated through an application describing statistically significant "synergy regions" for candidate drug combinations targeting epidermal growth factor receptor and the insulin-like growth factor 1 receptor.

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“…For a long time, a number of studies have noticed a crosstalk between the IGF-1 and EGFR signaling pathways [21], [22], [23]. Their synergistic interactions are thought to be associated with the acquired resistance to EGFR-tyrosine kinase inhibitors like gefitinib [22].…”

Section: Chiefly Produced By Receptor Functionmentioning

confidence: 99%

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Ray

2017

Hormone Molecular Biology and Clinical Investigation

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Abstract:Obesity is associated with the risk of several health disorders including certain cancers. Among obesity-related cancers, postmenopausal breast carcinoma is a well-studied one. Apart from an increase in certain types of lipids in obesity, excess adipose tissue releases many hormone-like cytokines/adipokines, which are usually pro-inflammatory in nature. Leptin is one of such adipokines and significantly linked with the intracellular signaling pathways of other growth factors such as insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2). In general, HER2 is overexpressed in roughly 30% of breast carcinomas; its presence indicates aggressive tumor behavior. Conversely, HER2 has certain effects in normal conditions such as differentiation of preadipocytes, cardiovascular health and vitamin D metabolism. HER2 has no known endogenous ligand, but it may form dimers with other three members of the epidermal growth factor receptor (EGFR) family and can activate downstream signaling pathways. Furthermore, HER2 is intimately connected with several enzymes, e.g. fatty acid synthase (FASN), phosphatidylinositol 3-kinase (PI3K), AKT and mechanistic target of rapamycin (mTOR), all of which play significant regulatory roles in lipogenic pathways or lipid metabolism. In obesity-related carcinogenesis, characteristics like insulin resistance and elevated IGF-1 are commonly observed. Both IGF-1 and leptin can modulate EGFR and HER2 signaling pathways. Although clinical studies have shown mixed results, the behavior of HER2+ tumor cells including HER2 levels can be altered by several factors such as obesity, leptin and fatty acids. A precise knowledge is useful in new therapeutic approaches against HER+ tumors.

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Activation of the Insulin-like Growth Factor-1 Receptor Induces Resistance to Epidermal Growth Factor Receptor Antagonism in Head and Neck Squamous Carcinoma Cells

Cited by 75 publications

References 36 publications

Prognostic significance of the tumour-adjacent tissue in head and neck cancers

Prognostic significance of the tumour-adjacent tissue in head and neck cancers

A New Bliss Independence Model to Analyze Drug Combination Data

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

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