ArticleCell cycle (Georgetown, Tex.)2012
Disruption of the protein interaction between FAK and IGF-1R inhibits melanoma tumor growth.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
The trial behind it
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Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- Focal adhesion kinase (FAK): emerging target for drug-resistant malignant tumors.Molecular biology reports · 2025Review
- Novel dual-targeting inhibitors of NSD2 and HDAC2 for the treatment of liver cancer: structure-based virtual screening, molecular dynamics simulation, andJournal of enzyme inhibition and medicinal chemistry · 2024Article
- Review
- Roles and inhibitors of FAK in cancer: current advances and future directions.Frontiers in pharmacology · 2024Review
- Current status and future perspectives in HER2 positive advanced gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: where do we stand?Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Review
- IGF1R and Src inhibition induce synergistic cytotoxicity in HNSCC through inhibition of FAK.Scientific reports · 2021Article
- FAK displacement from focal adhesions: a promising strategy to target processes implicated in cancer progression and metastasis.Cell communication and signaling : CCS · 2021Article
- FAK Signaling in Rhabdomyosarcoma.International journal of molecular sciences · 2020Review
- Targeting the Extra-Cellular Matrix-Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors.Frontiers in oncology · 2020Review
- Review
- Preparation,RSC advances · 2018Article
- The transcription factor RUNX2 regulates receptor tyrosine kinase expression in melanoma.Oncotarget · 2016Article
- Multiple Molecular Pathways in Melanomagenesis: Characterization of Therapeutic Targets.Frontiers in oncology · 2015Review
- Emerging roles of focal adhesion kinase in cancer.BioMed research international · 2015Review
- The role of FAK in tumor metabolism and therapy.Pharmacology & therapeutics · 2014Review
- Expressions of miR-22 and miR-135a in acute pancreatitis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2014Article
- A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells.Cell cycle (Georgetown, Tex.) · 2014Article
- A FAK scaffold inhibitor disrupts FAK and VEGFR-3 signaling and blocks melanoma growth by targeting both tumor and endothelial cells.Cell cycle (Georgetown, Tex.) · 2014Article
- Targeting FAK in human cancer: from finding to first clinical trials.Frontiers in bioscience (Landmark edition) · 2014Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
FAK (focal adhesion kinase) and IGF-1R (insulin-like growth factor receptor-1) directly interact with each other and thereby activate crucial signaling pathways that benefit cancer cells. Inhibition of FAK and IGF-1R function has been shown to significantly decrease cancer cell proliferation and increase sensitivity to chemotherapy and radiation treatment. As a novel approach in human melanoma, we evaluated the effect of a small-molecule compound that disrupts the protein interaction of FAK and IGF-1R. Previously, using virtual screening and functional testing, we identified a lead compound (INT2-31) that targets the known FAK-IGF-1R protein interaction site. We studied the ability of this compound to disrupt FAK-IGF-1R protein interactions, inhibit downstream signaling, decrease human melanoma cell proliferation, alter cell cycle progression, induce apoptosis and decrease tumor growth in vivo. INT2-31 blocked the interaction of FAK and IGF-1R in vitro and in vivo in melanoma cells and tumor xenografts through precluding the activation of IRS-1, leading to reduced phosphorylation of AKT upon IGF-1 stimulation. As a result, INT2-31 significantly inhibited cell proliferation and viability (range 0.05-10 μM). More importantly, 15 mg/kg of INT2-31 given for 21 d via intraperitoneal injection disrupted the interaction of FAK and IGF-1R and effectively decreased phosphorylation of tumor AKT, resulting in significant melanoma tumor regression in vivo. Our data suggest that the FAK-IGF-1R protein interaction is an important target, and disruption of this interaction with a novel small molecule (INT2-31) has potential anti-neoplastic therapeutic effects in human melanoma.
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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 Socratic graph.