ArticleOncotarget2016
Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Emerging role of IGF1R and IR expression and localisation in adrenocortical carcinomas.Cell communication and signaling : CCS · 2025Article
- Therapeutic strategies for adrenocortical carcinoma: integrating genomic insights, molecular targeting, and immunotherapy.Frontiers in immunology · 2025Review
- IGF-1R targeting in cancer - does sub-cellular localization matter?Journal of experimental & clinical cancer research : CR · 2023Review
- Expression of EMP 1, 2, and 3 in Adrenal Cortical Neoplasm and Pheochromocytoma.International journal of molecular sciences · 2023Article
- An insulin growth factor-I/II-neutralizing monoclonal antibody in combination with epidermal growth factor receptor inhibitors potently inhibits tumor cell growth.Journal of Cancer · 2022Article
- Apoptosis regulation in adrenocortical carcinoma.Endocrine connections · 2019Review
- The role of epithelial growth factors and insulin growth factors in the adrenal neoplasms.Annals of translational medicine · 2018Review
- Inhibition of PI3K/Akt/mTOR overcomes cisplatin resistance in the triple negative breast cancer cell line HCC38.BMC cancer · 2017Article
- Cell signaling pathways in the adrenal cortex: Links to stem/progenitor biology and neoplasia.Molecular and cellular endocrinology · 2017Review
- Formal modeling and analysis of ER-PeerJ · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAdrenocortical carcinoma (ACC) is a rare tumor with very poor prognosis and no effective treatment. The aim of this study was to explore a novel therapy co-targeting EGFR and IGF1R in vitro and vivo.
methodsThe expression of EGFR and IGF1R were evaluated in a series of adrenocortical tumors by immunohistochemistry. Cell viability of ACC cell lines H295R and SW13 were determined by MTT assay after treatment with the combination of EGFR inhibitor Erlotinib and IGF1R inhibitor NVP-AEW541. Apoptosis was assessed by flow cytometry. The mechanism within intracellular signaling pathways was analyzed by Western blot. Mice bearing human ACC xenografts were treated with Erlotinib and NVP-AEW541, and the effects on tumour growth were assessed.
resultsOur results show a significant over-expression of EGFR (66.67%) and IGF1R (80.0%) in ACC. Besides, the co-overexpression of EGFR and IGF1R was seen in 8/15 ACCs, as compared with ACAs (P<0.05). Erlotinib and NVP-AEW541 significantly inhibited cell viability and induced apoptosis by blocking phosphorylation of MEK/ERK and AKT, respectively. Meanwhile, we found that single inhibition of IGF1R induced compensatory activation of MEK/ERK, leading to sustained activation of mTOR, which represent as aggregation of EGFR and IGF1R downstream components. More importantly, the combination of Erlotinib and NVP-AEW541 enhances anti-tumour efficacy compared to treatment with either agent alone or to untreated control in vitro and vivo.
conclusionsIn conclusion, coinhibition therapy targeting EGFR and IGF1R may be considerable for treatment of ACC in the future.
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