ArticleNeoplasia (New York, N.Y.)2015
IGF-1R Inhibition Activates a YES/SFK Bypass Resistance Pathway: Rational Basis for Co-Targeting IGF-1R and Yes/SFK Kinase in Rhabdomyosarcoma.
Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Paediatric Therapeutic Development Workshop on rhabdomyosarcoma.British journal of cancer · 2026Review
- Molecular Targets in Alveolar Rhabdomyosarcoma: A Narrative Review of Progress and Pitfalls.International journal of molecular sciences · 2025Review
- Myogenic IGFBP5 levels in rhabdomyosarcoma are nourished by mesenchymal stromal cells and regulate growth arrest and apoptosis.Cell communication and signaling : CCS · 2025Article
- Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches.International journal of molecular sciences · 2024Review
- The Capacity of Drug-Metabolising Enzymes in Modulating the Therapeutic Efficacy of Drugs to Treat Rhabdomyosarcoma.Cancers · 2024Review
- Statin-Sensitive Akt1/Src/Caveolin-1 Signaling Enhances Oxidative Stress Resistance in Rhabdomyosarcoma.Cancers · 2024Article
- Phase I trial of Ganitumab plus Dasatinib to Cotarget the Insulin-Like Growth Factor 1 Receptor and Src Family Kinase YES in Rhabdomyosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Network Analysis for the Discovery of Common Oncogenic Biomarkers in Liver Cancer Experimental Models.Biomedicines · 2023Article
- The Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Strongylopus grayii tadpole blastema extract exerts cytotoxic effects on embryonal rhabdomyosarcoma cells.In vitro cellular & developmental biology. Animal · 2022Article
- Phosphoproteomic profiling of T cell acute lymphoblastic leukemia reveals targetable kinases and combination treatment strategies.Nature communications · 2022Article
- Review
- Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children's Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force.Journal of clinical medicine · 2021Review
- Relapsed Rhabdomyosarcoma.Journal of clinical medicine · 2021Review
- Development of the phenylpyrazolo[3,4-Theranostics · 2021Article
- Integrin and autocrine IGF2 pathways control fasting insulin secretion in β-cells.The Journal of biological chemistry · 2020Article
- Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy.Journal of hematology & oncology · 2020Review
- Targeting the undruggable: exploiting neomorphic features of fusion oncoproteins in childhood sarcomas for innovative therapies.Cancer metastasis reviews · 2019Review
- Insights into pediatric rhabdomyosarcoma research: Challenges and goals.Pediatric blood & cancer · 2019Review
- Genetics, epigenetics and redox homeostasis in rhabdomyosarcoma: Emerging targets and therapeutics.Redox biology · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The insulin-like growth factor 1 receptor (IGF-1R) has surfaced as a significant target in multiple solid cancers due to its fundamental roles in pro-survival and anti-apoptotic signaling. However, development of resistance to IGF-1R blockade represents a significant hindrance and limits treatment efficacy in the clinic. In this study, we identified acquired resistance to IGF-1R blockade with R1507, an antibody against IGF-1R, and with BMS-754807, a small molecular inhibitor of IGF-1R/insulin receptor (IR). We showed that treatment with an IGF-IR antibody, R1507, or an IR/IGF-IR kinase inhibitor, BMS-754807, was associated with increased activation of YES/SRC family tyrosine kinase (SFK) in rhabdomyosarcoma (RMS). Combining anti-IGF-1R agents with SFK inhibitors resulted in blockade of IGF-1R inhibition-induced activation of YES/SFK and displayed advantageous antitumor activity in vitro and in vivo. Our data provide evidence that IGF-1R blockade results in activation of the YES/SRC family kinase bypass resistance pathway in vitro and in vivo. This may be of particular clinical relevance since both Yes and IGF components are overexpressed in RMS. Increased YES/SFK activation might serve as a clinical biomarker for predicting tumor resistance to IGF-1R inhibition. Dual inhibition of IGF-1R and SFK may have a broader and enhanced clinical benefit for patients with RMS.
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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.