ArticlePloS one2011
R1507, an anti-insulin-like growth factor-1 receptor (IGF-1R) antibody, and EWS/FLI-1 siRNA in Ewing's sarcoma: convergence at the IGF/IGFR/Akt axis.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 39 citations in OpenAlex.
- Phase I study of sapanisertib with carboplatin and paclitaxel in mTOR pathway altered solid malignancies.NPJ precision oncology · 2023Review
- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- Review
- IGF Signaling in Intervertebral Disc Health and Disease.Frontiers in cell and developmental biology · 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
- Transcriptome profiling of Ewing sarcomas - treatment resistance pathways and IGF-dependency.Molecular oncology · 2020Article
- The Role of Tyrosine Kinases as a Critical Prognostic Parameter and Its Targeted Therapies in Ewing Sarcoma.Frontiers in cell and developmental biology · 2020Review
- IGF1 receptor and thyroid-associated ophthalmopathy.Journal of molecular endocrinology · 2018Review
- Article
- PI3K/AKT signaling modulates transcriptional expression of EWS/FLI1 through specificity protein 1.Oncotarget · 2015Article
- Can we unlock the potential of IGF-1R inhibition in cancer therapy?Cancer treatment reviews · 2014Review
- Teprotumumab, an IGF-1R blocking monoclonal antibody inhibits TSH and IGF-1 action in fibrocytes.The Journal of clinical endocrinology and metabolism · 2014Article
- Let-7a functions as a tumor suppressor in Ewing's sarcoma cell lines partly by targeting cyclin-dependent kinase 6.DNA and cell biology · 2014Article
- Novel secondary somatic mutations in Ewing's sarcoma and desmoplastic small round cell tumors.PloS one · 2014Article
- Preclinical evaluation of the PARP inhibitor, olaparib, in combination with cytotoxic chemotherapy in pediatric solid tumors.Pediatric blood & cancer · 2014Article
- Significant association between cytotoxic T lymphocyte antigen 4 +49G>A polymorphism and risk of malignant bone tumors.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- Prognostic and therapeutic relevance of the IGF pathway in Ewing's sarcoma patients.Targeted oncology · 2013Article
- Children's Oncology Group's 2013 blueprint for research: bone tumors.Pediatric blood & cancer · 2013Review
- A kinase-independent biological activity for insulin growth factor-1 receptor (IGF-1R) : implications for inhibition of the IGF-1R signal.Oncotarget · 2013Article
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
A subset of patients with Ewing's sarcoma responds to anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies. Mechanisms of sensitivity and resistance are unknown. We investigated whether an anti-IGF-1R antibody acts via a pathway that could also be suppressed by small interfering (si) RNA against the EWS/FLI-1 fusion protein, the hallmark of Ewing's sarcoma. The growth of two Ewing's sarcoma cell lines (TC-32 and TC-71) was inhibited by the fully human anti-IGF-1R antibody, R1507 (clonogenic and MTT assays). TC-32 and TC-71 cells express high levels of IGF-2, while RD-ES and A4573 Ewing's cell lines, which were less responsive to R1507 in our assays, express low or undetectable IGF-2, respectively. TC-71 cells also expressed high levels of IGF-1R, and R1507 decreased steady-state levels of this receptor by internalization/degradation, an effect which was associated with a decrease in p-IGF-1R, p-IRS-1, and p-Akt. EWS/FLI-1 siRNA also decreased p-Akt, due to its ability to increase IGF-BP3 levels and subsequently decrease IGF-1 and IGF-2 levels, thus inhibiting signaling through p-IGF-1R. This inhibition correlated with growth suppression and apoptosis. The attenuation of Akt activation was confirmed in TC-71 and HEK-293 (human embryonic kidney) cells by transfecting them with IGF-1R siRNA. We conclude that antibodies and siRNA to IGF-1R, as well as siRNA to EWS/FLI-1, act via intersecting IGF/IGF-1R signals that suppress a common point in this pathway, namely the phosphorylation of Akt.
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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.