ArticleProceedings of the National Academy of Sciences of the United States of America2012
Dependence of Wilms tumor cells on signaling through insulin-like growth factor 1 in an orthotopic xenograft model targetable by specific receptor inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 34 citations in OpenAlex.
- The insulin receptor inhibitor BMS-754807 alleviates neuroinflammation and Alzheimer's disease pathologies across human cellular and mouse models.Journal of neuroinflammation · 2026Article
- Hallmark discoveries in the biology of Wilms tumour.Nature reviews. Urology · 2024Review
- Retinoic acid promotes differentiation of WiT49- but not of CCG99-11 Wilms tumour cells.Cancer reports (Hoboken, N.J.) · 2023Article
- The epithelial splicing regulator ESRP2 is epigenetically repressed by DNA hypermethylation in Wilms tumour and acts as a tumour suppressor.Molecular oncology · 2022Article
- Article
- 17β-Estradiol promotes endometrial cancer proliferation and invasion through IL-6 pathway.Endocrine connections · 2019Article
- miR-140-5p could suppress tumor proliferation and progression by targeting TGFBRI/SMAD2/3 and IGF-1R/AKT signaling pathways in Wilms' tumor.BMC cancer · 2019Article
- The Iroquois homeobox proteins IRX3 and IRX5 have distinct roles in Wilms tumour development and human nephrogenesis.The Journal of pathology · 2019Article
- Mutations in microRNA processing genes in Wilms tumors derepress theGenes & development · 2018Article
- Pre-clinical imaging of transgenic mouse models of neuroblastoma using a dedicated 3-element solenoid coil on a clinical 3T platform.British journal of cancer · 2017Article
- Functional KRAS mutations and a potential role for PI3K/AKT activation in Wilms tumors.Molecular oncology · 2017Article
- Article
- Clinical next-generation sequencing reveals aggressive cancer biology in adolescent and young adult patients.Oncoscience · 2015Article
- Context Sensitive Modeling of Cancer Drug Sensitivity.PloS one · 2015Article
- Article
- The IGF signalling pathway in Wilms tumours--a report from the ENCCA Renal Tumours Biology-driven drug development workshop.Oncotarget · 2014Article
- Activation of Ras overcomes B-cell tolerance to promote differentiation of autoreactive B cells and production of autoantibodies.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Type 1 insulin-like growth factor receptor targeted therapies in pediatric cancer.Frontiers in oncology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
We have previously demonstrated an increased DNA copy number and expression of IGF1R to be associated with poor outcome in Wilms tumors. We have now tested whether inhibiting this receptor may be a useful therapeutic strategy by using a panel of Wilms tumor cell lines. Both genetic and pharmacological targeting resulted in inhibition of downstream signaling through PI3 and MAP kinases, G(1) cell cycle arrest, and cell death, with drug efficacy dependent on the levels of phosphorylated IGF1R. These effects were further associated with specific gene expression signatures reflecting pathway inhibition, and conferred synergistic chemosensitisation to doxorubicin and topotecan. In the in vivo setting, s.c. xenografts of WiT49 cells resembled malignant rhabdoid tumors rather than Wilms tumors. Treatment with an IGF1R inhibitor (NVP-AEW541) showed no discernable antitumor activity and no downstream pathway inactivation. By contrast, Wilms tumor cells established orthotopically within the kidney were histologically accurate and exhibited significantly elevated insulin-like growth factor-mediated signaling, and growth was significantly reduced on treatment with NVP-AEW541 in parallel with signaling pathway ablation. As a result of the paracrine effects of enhanced IGF2 expression in Wilms tumor, this disease may be acutely dependent on signaling through the IGF1 receptor, and thus treatment strategies aimed at its inhibition may be useful in the clinic. Such efficacy may be missed if only standard ectopic models are considered as a result of an imperfect recapitulation of the specific tumor microenvironment.
Indexed as
Identifiers
What OpenQuestion holds
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.