ArticleMolecular cancer therapeutics2012
Targeting the insulin growth factor and the vascular endothelial growth factor pathways in ovarian cancer.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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
14 citing papers in PubMed, 33 citations in OpenAlex.
- Metformin Impairs Linsitinib Anti-Tumor Effect on Ovarian Cancer Cell Lines.International journal of molecular sciences · 2024Article
- NEU4-mediated desialylation enhances the activation of the oncogenic receptors for the dissemination of ovarian carcinoma.Oncogene · 2024Article
- Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins.International journal of molecular sciences · 2023Review
- New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay.Advanced healthcare materials · 2023Article
- Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed.Frontiers in immunology · 2022Review
- Effects of Intravitreal Aflibercept on the Systemic Insulin-like Growth Factor-I and Vascular Endothelial Growth Factor-A in Patients with Diabetic Retinopathy and Age-Related Macular Degeneration.Journal of ophthalmology · 2021Article
- The Role of the Insulin-Like Growth Factor 1 Pathway in Immune Tumor Microenvironment and Its Clinical Ramifications in Gynecologic Malignancies.Frontiers in endocrinology · 2018Article
- Nucleus accumbens-associated protein-1 promotes glycolysis and survival of hypoxic tumor cells via the HDAC4-HIF-1α axis.Oncogene · 2017Article
- Targeting human vasohibin-2 by a neutralizing monoclonal antibody for anti-cancer treatment.Cancer science · 2017Article
- Gene expression levels of the insulin-like growth factor family in patients with AMD before and after ranibizumab intravitreal injections.Clinical interventions in aging · 2017Article
- The Role of the Insulin/IGF System in Cancer: Lessons Learned from Clinical Trials and the Energy Balance-Cancer Link.Frontiers in endocrinology · 2015Review
- The links between insulin resistance, diabetes, and cancer.Current diabetes reports · 2013Review
- Recent progress in genetics of aging, senescence and longevity: focusing on cancer-related genes.Oncotarget · 2012Review
- Role of Insulin-like Growth Factor, Insulin-like Growth Factor Receptors, and Insulin-like Growth Factor-binding Proteins in Ovarian Cancer.Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric OncologyReview
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Antiangiogenic therapy is emerging as a highly promising strategy for the treatment of ovarian cancer, but the clinical benefits are usually transitory. The purpose of this study was to identify and target alternative angiogenic pathways that are upregulated in ovarian xenografts during treatment with bevacizumab. For this, angiogenesis-focused gene expression arrays were used to measure gene expression levels in SKOV3 and A2780 serous ovarian xenografts treated with bevacizumab or control. Reverse transcription-PCR was used for results validation. The insulin growth factor 1 (IGF-1) was found upregulated in tumor and stromal cells in the two ovarian xenograft models treated with bevacizumab. Cixutumumab was used to block IGF-1 signaling in vivo. Dual anti-VEGF and IGF blockade with bevacizumab and cixutumumab resulted in increased inhibition of tumor growth. Immunohistochemistry measured multivessel density, Akt activation, and cell proliferation, whereas terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay measured apoptosis in ovarian cancer xenografts. Bevacizumab and cixutumumab combination increased tumor cell apoptosis in vivo compared with therapy targeting either individual pathway. The combination blocked angiogenesis and cell proliferation but not more significantly than each antibody alone. In summary, IGF-1 activation represents an important mechanism of adaptive escape during anti-VEGF therapy in ovarian cancer. This study provides the rationale for designing bevacizumab-based combination regimens to enhance antitumor activity.
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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.