ArticleAmerican journal of cancer research2015
Targeting oncogenic KRAS in non-small cell lung cancer cells by phenformin inhibits growth and angiogenesis.
Article in American journal of cancer research, 2015. 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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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Association of pre-existing conditions with major driver mutations and PD-L1 expression in NSCLC.BMJ open respiratory research · 2024Article
- Progress in antitumor mechanisms and applications of phenformin (Review).Oncology reports · 2024Review
- Impact of KRAS mutation on the tumor microenvironment in colorectal cancer.International journal of biological sciences · 2024Review
- Repurposing Metabolic Inhibitors in the Treatment of Colon Adenocarcinoma Patient-Derived Models.Cells · 2023Article
- Case report: long-term sustained remission in a case of metastatic colon cancer with high microsatellite instability and KRAS exon 2 p.G12D mutation treated with fruquintinib after local radiotherapy: a case report and literature review.Frontiers in pharmacology · 2023Article
- Cytotoxicity of combinations of the pan-KRAS SOS1 inhibitor BAY-293 against pancreatic cancer cell lines.Discover oncology · 2022Article
- Mediating EGFR-TKI Resistance by VEGF/VEGFR Autocrine Pathway in Non-Small Cell Lung Cancer.Cells · 2022Article
- Cytotoxicity of combinations of the pan-KRAS inhibitor BAY-293 against primary non-small lung cancer cells.Translational oncology · 2021Article
- The up-regulation of miR-21 by gastrodin to promote the angiogenesis ability of human umbilical vein endothelial cells by activating the signaling pathway of PI3K/Akt.Bioengineered · 2021Article
- Current progress and future perspectives of polypharmacology : From the view of non-small cell lung cancer.Seminars in cancer biology · 2021Review
- Phenformin synergistically sensitizes liver cancer cells to sorafenib by downregulating CRAF/ERK and PI3K/AKT/mTOR pathways.American journal of translational research · 2021Article
- Quinazoline Derivatives as Potential Therapeutic Agents in Urinary Bladder Cancer Therapy.Frontiers in chemistry · 2021Review
- Loss ofCancers · 2020Article
- Iatrogenic endometriosis harbors somatic cancer-driver mutations.Human reproduction (Oxford, England) · 2019Article
- Phenformin alone or combined with gefitinib inhibits bladder cancer via AMPK and EGFR pathways.Cancer communications (London, England) · 2018Article
- Blocking transferrin receptor inhibits the growth of lung adenocarcinoma cells in vitro.Thoracic cancer · 2018Article
- MicroRNAs Associated with Von Hippel-Lindau Pathway in Renal Cell Carcinoma: A Comprehensive Review.International journal of molecular sciences · 2017Review
- Statistically controlled identification of differentially expressed genes in one-to-one cell line comparisons of the CMAP database for drug repositioning.Journal of translational medicine · 2017Article
- Results fromScientific reports · 2017Article
- Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications.Chemical reviews · 2017Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumors require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors. Many potential oncogenic mutations have been identified in tumor angiogenesis. Somatic mutations in the small GTPase KRAS are the most common activating lesions found in human cancer, and are generally associated with poor response to standard therapies. Biguanides, such as the diabetes therapeutics metformin and phenformin, have demonstrated anti-tumor activity both in vitro and in vivo. The extracellular regulated protein kinases (ERK) signaling is known to be a major cellular target of biguanides. Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo. In cancer cells harboring oncogenic KRAS, phenformin switches off the ERK pathway and inhibit the expression of pro-angiogenic molecules. In tumor xenografts harboring the KRAS mutation, phenformin extensively modifies the tumor growth causing abrogation of angiogenesis. These results strongly suggest that significant therapeutic advantage may be achieved by phenformin anti-angiogenesis for the treatment of tumor.
Indexed as
Identifiers
26807315PMC4697681W2410446908What 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.