ArticleCancers2021
IGF1R/IR Mediates Resistance to BRAF and MEK Inhibitors in BRAF-Mutant Melanoma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 32 citations in OpenAlex.
- Dynamic Time-Resolved Remodeling of the Immune Microenvironment After Resistance to BRAF/MEK Inhibitors in Melanoma: Mechanisms, Biomarkers, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Association of serum vitamin D and serum vitamin C with the risk of melanoma among adults in the United States: a cross-sectional analysis of 2003-2006 and 2017-2018 NHANES data.Journal of clinical biochemistry and nutrition · 2026Article
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Anoikis classification of lung squamous cell carcinoma reveals correlation with clinical prognosis and immune characteristics.Annals of medicine · 2025Article
- IGF-1R inhibitors in cancer: A review of available evidence and future outlook.Critical reviews in oncology/hematology · 2025Review
- Targeting Surface Markers in Anaplastic Thyroid Cancer: Future Directions in Ligand-bound Therapy.Journal of the Endocrine Society · 2025Review
- Inhibiting melanoma tumor growth: the role of oxidative stress-associatedFrontiers in immunology · 2025Article
- Pan-cancer analysis of prognostic and immunological role of IL4I1 in human tumors: a bulk omics research and single cell sequencing validation.Discover oncology · 2024Article
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2.International journal of molecular sciences · 2023Review
- Trametinib-Resistant Melanoma Cells Displaying MITFInternational journal of molecular sciences · 2023Article
- Efficient prioritization of CRISPR screen hits by accounting for targeting efficiency of guide RNA.BMC biology · 2023Article
- Comprehensive bioinformatics analysis reveals the crosstalk genes and immune relationship between the systemic lupus erythematosus and venous thromboembolism.Frontiers in immunology · 2023Article
- Epigenetic Mechanisms Underlying Melanoma Resistance to Immune and Targeted Therapies.Cancers · 2022Review
- The future of targeted kinase inhibitors in melanoma.Pharmacology & therapeutics · 2022Review
- Potential Biomarkers of Skin Melanoma Resistance to Targeted Therapy-Present State and Perspectives.Cancers · 2022Review
- Identification of IGF1R mutation as a novel predictor of efficacious immunotherapy in melanoma.Journal of translational medicine · 2022Article
- Nuclear interaction of Arp2/3 complex and BRAFAmerican journal of cancer research · 2022Article
- The Evolution of BRAF Activation in Non-Small-Cell Lung Cancer.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The use of BRAF and MEK inhibitors for patients with BRAF-mutant melanoma is limited as patients relapse on treatment as quickly as 6 months due to acquired resistance. We generated trametinib and dabrafenib resistant melanoma (TDR) cell lines to the MEK and BRAF inhibitors, respectively. TDR cells exhibited increased viability and maintenance of downstream p-ERK and p-Akt as compared to parental cells. Receptor tyrosine kinase arrays revealed an increase in p-IGF1R and p-IR in the drug resistant cells versus drug sensitive cells. RNA-sequencing analysis identified IGF1R and INSR upregulated in resistant cell lines compared to parental cells. Analysis of TCGA PanCancer Atlas (skin cutaneous melanoma) showed that patients with a BRAF mutation and high levels of IGF1R and INSR had a worse overall survival. BMS-754807, an IGF1R/IR inhibitor, suppressed cell proliferation along with inhibition of intracellular p-Akt in TDR cells. Dual inhibition of IGF1R and INSR using siRNA reduced cell proliferation. The combination of dabrafenib, trametinib, and BMS-754807 treatment reduced in vivo xenograft tumor growth. Examining the role of IGF1R and IR in mediating resistance to BRAF and MEK inhibitors will expand possible treatment options to aid in long-term success for BRAF-mutant melanoma patients.
Indexed as
Identifiers
What Socratic 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 Socratic graph.