ArticleEndocrine2019
IGF and mTOR pathway expression and in vitro effects of linsitinib and mTOR inhibitors in adrenocortical cancer.
Article in Endocrine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- IGF2R: a new player in the IGF2 loop sustaining adrenocortical carcinogenesis.Cell communication and signaling : CCS · 2026Article
- Engineered nanoparticles for endocrine tumor targeting, current progress and future outlook.Medical oncology (Northwood, London, England) · 2025Review
- The Cytoskeleton in Adrenal Physiology and Tumours: Functional Roles and Emerging Molecular Targets.International journal of molecular sciences · 2025Review
- SorCS3 suppresses adrenocortical carcinoma progression by enhancing IGF2R-mediated endocytic trafficking and signaling attenuation.Journal of translational medicine · 2025Article
- Emerging role of IGF1R and IR expression and localisation in adrenocortical carcinomas.Cell communication and signaling : CCS · 2025Article
- Zuogui Pill Promotes Neurite Outgrowth by Regulating OPN/ IGF-1R/PTEN and Downstream mTOR Signaling Pathway.Combinatorial chemistry & high throughput screening · 2025Article
- Review
- Development and Characterization of 3-Dimensional Cell Culture Models of Adrenocortical Carcinoma.Endocrinology · 2024Article
- Single-nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands.Clinical and translational medicine · 2024Article
- Linsitinib inhibits proliferation and induces apoptosis of both IGF-1R and TSH-R expressing cells.Frontiers in immunology · 2024Article
- Editorial: Adipokines and hormone-dependent cancers.Frontiers in endocrinology · 2023Article
- Obesity and endocrine-related cancer: The important role of IGF-1.Frontiers in endocrinology · 2023Review
- Review
- Adrenocortical carcinoma: Pediatric aspects (Review).Experimental and therapeutic medicine · 2022Review
- Role of filamin A in the pathogenesis of neuroendocrine tumors and adrenal cancer.Endocrine oncology (Bristol, England) · 2022Review
- Review
- Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance.Biomedicines · 2021Review
- The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives.Biomedicines · 2021Review
- The Interplay Between Non-coding RNAs and Insulin-Like Growth Factor Signaling in the Pathogenesis of Neoplasia.Frontiers in cell and developmental biology · 2021Review
- Management of adrenocortical carcinoma: are we making progress?Therapeutic advances in medical oncology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe IGF and mTOR-pathways are considered as potential targets for therapy in patients with adrenocortical carcinoma (ACC). This study aims to describe the IGF pathway in ACC and to explore the response to the combined treatment with the IGF1R/IR inhibitor linsitinib, and mTOR inhibitors (sirolimus and everolimus) in in vitro models of ACC.
methodsThe protein expression level of IGF2, IGF1R and IGF2R was evaluated by immunohistochemistry in 17 human ACCs and the mRNA expression level of IGF1, IGF2, IGF1R, IR isoforms A and B, IGF2R, IGF-Binding-Proteins[IGFBP]-1, 2, 3 and 6 was evaluated by RT-qPCR in 12 samples. In H295R and HAC15 ACC cell lines the combined effects of linsitinib and sirolimus or everolimus on cell survival were evaluated.
resultsA high protein expression of IGF2, IGF1R and IGF2R was observed in 82, 65 and 100% of samples, respectively. A high relative expression of IGF2 mRNA was found in the majority of samples. The mRNA levels of the IRA were higher than that of IRB and IGF1R in the majority of samples (75%). Linsitinib inhibits cell growth in the H295R and HAC15 cell lines and, combined with sirolimus or everolimus, linsitinib showed a significant additive effect.
conclusionsIn addition to IGF2 and IGF1R, ACC express IGF2R, IRA and several IGFBPs, suggesting that the interplay between the different components of the IGF pathway in ACC could be more complex than previously considered. The addition of mTOR inhibitors to linsitinib may have stronger antiproliferative effects than linsitinib alone.
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