ArticleMolecular cancer research : MCR2014
PTEN deficiency mediates a reciprocal response to IGFI and mTOR inhibition.
Article in Molecular cancer research : MCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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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
18 citing papers in PubMed.
- Targeting autophagy and metabolism for ewing sarcoma.Molecular biology reports · 2025Review
- Co-targeting JAK1/STAT6/GAS6/TAM signaling improves chemotherapy efficacy in Ewing sarcoma.Nature communications · 2024Article
- IGF-1R targeting in cancer - does sub-cellular localization matter?Journal of experimental & clinical cancer research : CR · 2023Review
- Shifting from a Biological-Agnostic Approach to a Molecular-Driven Strategy in Rare Cancers: Ewing Sarcoma Archetype.Biomedicines · 2023Review
- The prognostic value of autophagy related genes with potential protective function in Ewing sarcoma.BMC bioinformatics · 2022Article
- The Controversial Role of Autophagy in Ewing Sarcoma Pathogenesis-Current Treatment Options.Biomolecules · 2021Review
- The Effectiveness of Sirolimus Treatment in Two Rare Disorders with Nonketotic Hypoinsulinemic Hypoglycemia: The Role of mTOR PathwayJournal of clinical research in pediatric endocrinology · 2020Article
- A computational strategy to understand structure-activity relationship of 1,3-disubstituted imidazole [1,5-α] pyrazine derivatives described as ATP competitive inhibitors of the IGF-1 receptor related to Ewing sarcoma.Journal of molecular modeling · 2020Article
- Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy.Journal of hematology & oncology · 2020Review
- The Role of Tyrosine Kinases as a Critical Prognostic Parameter and Its Targeted Therapies in Ewing Sarcoma.Frontiers in cell and developmental biology · 2020Review
- MicroRNAs and the Genetic Nexus of Brain Aging, Neuroinflammation, Neurodegeneration, and Brain Trauma.Aging and disease · 2019Review
- The regulatory role of aberrant Phosphatase and Tensin Homologue and Liver Kinase B1 on AKT/mTOR/c-Myc axis in pancreatic neuroendocrine tumors.Oncotarget · 2017Article
- MicroRNAs and the metabolic hallmarks of aging.Molecular and cellular endocrinology · 2017Review
- Involvement of IGF-2, IGF-1R, IGF-2R and PTEN in development of human tooth germ - an immunohistochemical study.Organogenesis · 2016Article
- High-throughput small molecule screen identifies inhibitors of aberrant chromatin accessibility.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Potential Therapeutic Targets in Uterine Sarcomas.Sarcoma · 2015Review
- Variable expression of PIK3R3 and PTEN in Ewing Sarcoma impacts oncogenic phenotypes.PloS one · 2015Article
- MicroRNAs as Mediators of the Ageing Process.Genes · 2014Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
unlabelledRecent evidence implicates the insulin-like growth factor (IGF) pathway in development of Ewing sarcoma, a highly malignant bone and soft-tissue tumor that primarily affects children and young adults. Despite promising results from preclinical studies of therapies that target this pathway, early-phase clinical trials have shown that a significant fraction of patients do not benefit, suggesting that cellular factors determine tumor sensitivity. Using FAIRE-seq, a chromosomal deletion of the PTEN locus in a Ewing sarcoma cell line was identified. In primary tumors, PTEN deficiency was observed in a large subset of cases, although not mediated by large chromosomal deletions. PTEN loss resulted in hyperactivation of the AKT signaling pathway. PTEN rescue led to decreased proliferation, inhibition of colony formation, and increased apoptosis. Strikingly, PTEN loss decreased sensitivity to IGF1R inhibitors but increased responsiveness to temsirolimus, a potent mTOR inhibitor, as marked by induction of autophagy. These results suggest that PTEN is lost in a significant fraction of primary tumors, and this deficiency may have therapeutic consequences by concurrently attenuating responsiveness to IGF1R inhibition while increasing activity of mTOR inhibitors. The identification of PTEN status in the tumors of patients with recurrent disease could help guide the selection of therapies. IMPLICATIONS: PTEN status in Ewing sarcoma affects cellular responses to IGFI and mTOR-directed therapy, thus justifying its consideration as a biomarker in future clinical trials.
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