ArticleOncology reports2014
In vivo analysis of insulin-like growth factor type 1 receptor humanized monoclonal antibody MK-0646 and small molecule kinase inhibitor OSI-906 in colorectal cancer.
Article in Oncology reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
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
23 citing papers in PubMed, 34 citations in OpenAlex.
- GNGT1 is a potential prognostic and immunologic biomarker in gastric cancer.Scientific reports · 2025Article
- Picropodophyllin, an IGF‑1 receptor inhibitor, enhances oxaliplatin efficacy in chemoresistant colorectal cancer HCT116 cells by reducing metastatic potential.Oncology letters · 2025Article
- Machine learning-based analysis identifies a 13-gene prognostic signature to improve the clinical outcomes of colorectal cancer.Journal of gastrointestinal oncology · 2024Article
- Linsitinib inhibits proliferation and induces apoptosis of both IGF-1R and TSH-R expressing cells.Frontiers in immunology · 2024Article
- Review
- Article
- The Insulin-like Growth Factor System and Colorectal Cancer.Life (Basel, Switzerland) · 2022Review
- Diabetes and Colorectal Cancer Risk: Clinical and Therapeutic Implications.Journal of diabetes research · 2022Review
- ER stress-related mRNA-lncRNA co-expression gene signature predicts the prognosis and immune implications of esophageal cancer.American journal of translational research · 2022Article
- Review
- IGF1-mediated HOXA13 overexpression promotes colorectal cancer metastasis through upregulating ACLY and IGF1R.Cell death & disease · 2021Article
- Overactivation of the IGF signalling pathway in osteosarcoma: a potential therapeutic target?The journal of pathology. Clinical research · 2021Article
- Predicting the Survival and Immune Landscape of Colorectal Cancer Patients Using an Immune-Related lncRNA Pair Model.Frontiers in genetics · 2021Article
- Correlation of PRL3 expression with colorectal cancer progression.Journal of surgical oncology · 2021Article
- Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines.Cancers · 2020Article
- Prognostic and therapeutic implications of NHERF1 expression and regulation in colorectal cancer.Journal of surgical oncology · 2020Article
- TGFβ and IGF1R signaling activates protein kinase A through differential regulation of ezrin phosphorylation in colon cancer cells.The Journal of biological chemistry · 2018Article
- Insulin-IGF signaling affects cell transformation in the BALB/c 3T3 cell model.Scientific reports · 2016Article
- Compounds from the marine sponge Cribrochalina vasculum offer a way to target IGF-1R mediated signaling in tumor cells.Oncotarget · 2016Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The development and characterization of effective anticancer drugs against colorectal cancer (CRC) is of urgent need since it is the second most common cause of cancer death. The study was designed to evaluate the effects of two IGF-1R antagonists, MK-0646, a recombinant fully humanized monoclonal antibody and OSI-906, a small molecule tyrosine kinase inhibitor on CRC cells. Xenograft study was performed on IGF-1R-dependent CRC cell lines for analyzing the antitumor activity of MK-0646 and OSI-906. Tumor proliferation and apoptosis were assessed using Ki67 and TUNEL assays, respectively. We also performed in vitro characterization of MK-0646 and OSI-906 treatment on CRC cells to identify mechanisms associated with drug-induced cell death. Exposure of the GEO and CBS tumor xenografts to MK-0646 or OSI-906 led to a decrease in tumor growth. TUNEL analysis showed an increase of approximately 45-55% in apoptotic cells in both MK-0646 and OSI-906 treated tumor samples. We report the novel finding that treatment with IGF-1R antagonists led to downregulation of X-linked inhibitor of apoptosis (XIAP) protein involved in cell survival and inhibition of cell death. In conclusion, IGF-1R antagonists (MK-0646 and OSI-906) demonstrated single agent inhibition of subcutaneous CRC xenograft growth. This was coupled to pro-apoptotic effects resulting in downregulation of XIAP and inhibition of cell survival. We report a novel mechanism by which MK-0646 and OSI-906 elicits cell death in vivo and in vitro. Moreover, these results indicate that MK-0646 and OSI-906 may be potential anticancer candidates for the treatment of patients with IGF-1R-dependent CRC.
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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.