ArticleOncotarget2016
IGF-1R inhibition sensitizes breast cancer cells to ATM-related kinase (ATR) inhibitor and cisplatin.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Acromegaly and breast cancer risk: evidence from a systematic review and meta-analysis.Frontiers in endocrinology · 2025Pooled it
- Loss of IGF-1R impairs DNA-PKcs recruitment to chromatin leading to defective end-joining.Molecular oncology · 2026Article
- Identification of Molecular Subtypes and Prognostic Features of Breast Cancer Based on TGF-β Signaling-related Genes.Cancer informatics · 2025Article
- Decoding the Role of Insulin-like Growth Factor 1 and Its Isoforms in Breast Cancer.International journal of molecular sciences · 2024Review
- Contrasting consequences of podocyte insulin-like growth factor 1 receptor inhibition.iScience · 2024Article
- Exogenous Metabolic Modulators Improve Response to Carboplatin in Triple-Negative Breast Cancer.Cells · 2024Article
- Role of Insulin-like Growth Factor-1 Receptor in Tobacco Smoking-Associated Lung Cancer Development.Biomedicines · 2024Review
- Insulin promotes growth in breast cancer cells through the type I IGF receptor in insulin receptor deficient cells.Experimental cell research · 2024Article
- The Role of ARID1A in the Nonestrogenic Modulation of IGF-1 Signaling.Molecular cancer research : MCR · 2022Article
- Radiotherapy alters expression of molecular targets in prostate cancer in a fractionation- and time-dependent manner.Scientific reports · 2022Article
- Article
- ActivationFrontiers in endocrinology · 2022Review
- DNA Damage Repair Inhibitor for Breast Cancer Treatment.Advances in experimental medicine and biology · 2021Article
- Depletion of insulin-like growth factor 1 receptor increases radiosensitivity in colorectal cancer.Journal of gastrointestinal oncology · 2020Article
- Review
- Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy.Journal of hematology & oncology · 2020Review
- Downregulation of IGF1R Expression Inhibits Growth and Enhances Cisplatin Sensitivity of Head and Neck Squamous Cell Carcinoma Cells In Vitro.Hormones & cancer · 2019Article
- Targeting ATR in cancer.Nature reviews. Cancer · 2018Review
- FES-related tyrosine kinase activates the insulin-like growth factor-1 receptor at sites of cell adhesion.Oncogene · 2018Article
- Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer.Oncotarget · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The complexity of the IGF-1 signalling axis is clearly a roadblock in targeting this receptor in cancer therapy. Here, we sought to identify mediators of resistance, and potential co-targets for IGF-1R inhibition. By using an siRNA functional screen with the IGF-1R tyrosine kinase inhibitor (TKI) BMS-754807 in MCF-7 cells we identified several genes encoding components of the DNA damage response (DDR) pathways as mediators of resistance to IGF-1R kinase inhibition. These included ATM and Ataxia Telangiectasia and RAD3-related kinase (ATR). We also observed a clear induction of DDR in cells that were exposed to IGF-1R TKIs (BMS-754807 and OSI-906) as indicated by accumulation of γ-H2AX, and phosphorylated Chk1. Combination of the IGF-1R/IR TKIs with an ATR kinase inhibitor VE-821 resulted in additive to synergistic cytotoxicity compared to either drug alone. In MCF-7 cells with stably acquired resistance to the IGF-1R TKI (MCF-7-R), DNA damage was also observed, and again, dual inhibition of the ATR kinase and IGF-1R/IR kinase resulted in synergistic cytotoxicity. Interestingly, dual inhibition of ATR and IGF-1R was more effective in MCF-7-R cells than parental cells. IGF-1R TKIs also potentiated the effects of cisplatin in a panel of breast cancer cell lines. Overall, our findings identify induction of DDR by IGF-1R kinase inhibition as a rationale for co-targeting the IGF-1R with ATR kinase inhibitors or cisplatin, particularly in cells with acquired resistance to TKIs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.