ArticlePloS one2013
Metformin as an adjuvant drug against pediatric sarcomas: hypoxia limits therapeutic effects of the drug.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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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
25 citing papers in PubMed, 46 citations in OpenAlex.
- Metformin Suppresses Stemness of Non-Small-Cell Lung Cancer Induced by Paclitaxel through FOXO3a.International journal of molecular sciences · 2023Article
- Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.Molecular cancer · 2023Review
- Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma.Cancers · 2022Review
- Subventricular zone adult mouse neural stem cells require insulin receptor for self-renewal.Stem cell reports · 2022Article
- Hypoxia and its therapeutic possibilities in paediatric cancers.British journal of cancer · 2021Review
- Chemoradiation impairs myofiber hypertrophic growth in a pediatric tumor model.Scientific reports · 2020Article
- Imatinib revives the therapeutic potential of metformin on ewing sarcoma by attenuating tumor hypoxic response and inhibiting convergent signaling pathways.Cancer letters · 2020Article
- Article
- Role of Altered Metabolic Microenvironment in Osteolytic Metastasis.Frontiers in cell and developmental biology · 2020Review
- A Humanized Bone Niche Model Reveals Bone Tissue Preservation Upon Targeting Mitochondrial Complex I in Pseudo-Orthotopic Osteosarcoma.Journal of clinical medicine · 2019Article
- Effects of metformin on tumor hypoxia and radiotherapy efficacy: a [EJNMMI research · 2019Article
- Metformin Suppresses Self-Renewal Ability and Tumorigenicity of Osteosarcoma Stem Cells via Reactive Oxygen Species-Mediated Apoptosis and Autophagy.Oxidative medicine and cellular longevity · 2019Article
- Article
- EZH2, HIF-1, and Their Inhibitors: An Overview on Pediatric Cancers.Frontiers in pediatrics · 2018Review
- How to Modulate Tumor Hypoxia for Preclinical In Vivo Imaging Research.Contrast media & molecular imaging · 2018Review
- Metabolic modulation of Ewing sarcoma cells inhibits tumor growth and stem cell properties.Oncotarget · 2017Article
- Anti-tumor effects of everolimus and metformin are complementary and glucose-dependent in breast cancer cells.BMC cancer · 2017Article
- Metformin displaysKorean journal of pediatrics · 2016Article
- Unexploited Antineoplastic Effects of Commercially Available Anti-Diabetic Drugs.Pharmaceuticals (Basel, Switzerland) · 2016Review
- Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis.PLoS biology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin, a well-known insulin-sensitizer commonly used for type 2 diabetes therapy, has recently emerged as potentially very attractive drug also in oncology. It is cheap, it is relatively safe and many reports have indicated effects in cancer prevention and therapy. These desirable features are particularly interesting for pediatric sarcomas, a group of rare tumors that have been shown to be dependent on IGF and insulin system for pathogenesis and progression. Metformin exerts anti-mitogenic activity in several cancer histotypes through several molecular mechanisms. In this paper, we analyzed its effects against osteosarcoma, Ewing sarcoma and rhabdomyosarcoma, the three most common pediatric sarcomas. Despite in vitro metformin gave remarkable antiproliferative and chemosensitizing effects both in sensitive and chemoresistant cells, its efficacy was not confirmed against Ewing sarcoma xenografts neither as single agent nor in combination with vincristine. This discrepancy between in vitro and in vivo effects may be due to hypoxia, a common feature of solid tumors. We provide evidences that in hypoxia conditions metformin was not able to activate AMPK and inhibit mTOR signaling, which likely prevents the inhibitory effects of metformin on tumor growth. Thus, although metformin may be considered a useful complement of conventional chemotherapy in normoxia, its therapeutic value in highly hypoxic tumors may be more limited. The impact of hypoxia should be considered when novel therapies are planned for pediatric sarcomas.
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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.