ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Overcoming IGF1R/IR resistance through inhibition of MEK signaling in colorectal cancer models.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 59 citations in OpenAlex.
- Combined inhibition of insulin growth factor 1 receptor and autophagy prevents colorectal cancer metastasis.Medical oncology (Northwood, London, England) · 2025Article
- Coordinated regulation of IGF1R by HIF1α and HIF2α enhances chemoresistance in glioblastoma.Frontiers in pharmacology · 2025Article
- Article
- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- Synergistic effects of complex drug combinations in colorectal cancer cells predicted by logical modelling.Frontiers in systems biology · 2023Article
- The drug-induced phenotypic landscape of colorectal cancer organoids.Nature communications · 2022Article
- Recent advances and limitations in the application of kahalalides for the control of cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Review
- Article
- Concurrent Inhibition of IGF1R and ERK Increases Pancreatic Cancer Sensitivity to Autophagy Inhibitors.Cancer research · 2022Article
- Conquering oncogenic KRAS and its bypass mechanisms.Theranostics · 2022Review
- Article
- Article
- Predicting the Survival and Immune Landscape of Colorectal Cancer Patients Using an Immune-Related lncRNA Pair Model.Frontiers in genetics · 2021Article
- Modeling Adaptive Resistance of KRAS Mutant Colorectal Cancer to MAPK Pathway Inhibitors with a Three-Dimensional Tumor Model.ACS pharmacology & translational science · 2020Article
- IGF-1R inhibition induces MEK phosphorylation to promote survival in colon carcinomas.Signal transduction and targeted therapy · 2020Article
- A multitargeted probe-based strategy to identify signaling vulnerabilities in cancers.The Journal of biological chemistry · 2019Article
- Article
- MEK inhibition induces MYOG and remodels super-enhancers in RAS-driven rhabdomyosarcoma.Science translational medicine · 2018Article
- Antitumor activity of the polo-like kinase inhibitor, TAK-960, against preclinical models of colorectal cancer.BMC cancer · 2018Article
- Predicting human clinical trial responses in mice.Molecular & cellular oncology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
purposeResults from clinical trials involving resistance to molecularly targeted therapies have revealed the importance of rational single-agent and combination treatment strategies. In this study, we tested the efficacy of a type 1 insulin-like growth factor receptor (IGF1R)/insulin receptor (IR) tyrosine kinase inhibitor, OSI-906, in combination with a mitogen-activated protein (MAP)-ERK kinase (MEK) 1/2 inhibitor based on evidence that the MAP kinase pathway was upregulated in colorectal cancer cell lines that were resistant to OSI-906. EXPERIMENTAL
designThe antiproliferative effects of OSI-906 and the MEK 1/2 inhibitor U0126 were analyzed both as single agents and in combination in 13 colorectal cancer cell lines in vitro. Apoptosis, downstream effector proteins, and cell cycle were also assessed. In addition, the efficacy of OSI-906 combined with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886) was evaluated in vivo using human colorectal cancer xenograft models.
resultsThe combination of OSI-906 and U0126 resulted in synergistic effects in 11 of 13 colorectal cancer cell lines tested. This synergy was variably associated with apoptosis or cell-cycle arrest in addition to molecular effects on prosurvival pathways. The synergy was also reflected in the in vivo xenograft studies following treatment with the combination of OSI-906 and selumetinib.
conclusionsResults from this study demonstrate synergistic antiproliferative effects in response to the combination of OSI-906 with an MEK 1/2 inhibitor in colorectal cancer cell line models both in vitro and in vivo, which supports the rational combination of OSI-906 with an MEK inhibitor in patients with colorectal cancer. Clin Cancer Res; 19(22); 6219-29. ©2013 AACR.
Indexed as
Identifiers
What 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.