ArticleMolecular cancer therapeutics2017
Targeting Insulin Receptor in Breast Cancer Using Small Engineered Protein Scaffolds.
Article in Molecular cancer therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 29 citations in OpenAlex.
- FLIPs: Genetically encoded molecular biosensors for functional imaging of cell signaling by linear dichroism microscopy.Science advances · 2026Article
- Engineering isoform-selective miniprotein binders to the fetal form of the insulin receptor.Protein engineering, design & selection : PEDS · 2026Article
- Predicting and Interpreting Protein Developability Via Transfer of Convolutional Sequence Representation.ACS synthetic biology · 2023Article
- Glucose-dependent effect of insulin receptor isoforms on tamoxifen antitumor activity in estrogen receptor-positive breast cancer cells.Frontiers in endocrinology · 2023Article
- ACBD3 Bioinformatic Analysis and Protein Expression in Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Article
- The Emerging Role of the Fetal Insulin Receptor in Hormone-refractory Breast Cancer.Endocrinology · 2021Review
- High-throughput developability assays enable library-scale identification of producible protein scaffold variants.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Disrupting Insulin and IGF Receptor Function in Cancer.International journal of molecular sciences · 2021Review
- Magnetic Bead-Immobilized Mammalian Cells Are Effective Targets to Enrich Ligand-Displaying Yeast.ACS combinatorial science · 2020Article
- Programmable Assembly of Adeno-Associated Virus-Antibody Composites for Receptor-Mediated Gene Delivery.Bioconjugate chemistry · 2020Article
- Lipoic acid decreases breast cancer cell proliferation by inhibiting IGF-1R via furin downregulation.British journal of cancer · 2020Article
- Article
- Molecular evolution of peptides by yeast surface display technology.MedChemComm · 2019Review
- Engineering an EGFR-binding Gp2 domain for increased hydrophilicity.Biotechnology and bioengineering · 2019Article
- Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.ACS combinatorial science · 2018Article
- Challenges in modulating insulin receptor signalling as a therapeutic strategy for cancer.The Indian journal of medical research · 2018Article
- Engineered Charge Redistribution of Gp2 Proteins through Guided Diversity for Improved PET Imaging of Epidermal Growth Factor Receptor.Bioconjugate chemistry · 2018Article
- Beyond antibody engineering: directed evolution of alternative binding scaffolds and enzymes using yeast surface display.Microbial cell factories · 2018Review
- uc.38 induces breast cancer cell apoptosis via PBX1.American journal of cancer research · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Insulin receptor (InsR) and the type I insulin-like growth factor (IGF1R) are homologous receptors necessary for signal transduction by their cognate ligands insulin, IGF-I and IGF-II. IGF1R mAbs, intended to inhibit malignant phenotypic signaling, failed to show benefit in patients with endocrine-resistant tumors in phase III clinical trials. Our previous work showed that in tamoxifen-resistant cells, IGF1R expression was lacking, but InsR inhibition effectively blocked growth. In endocrine-sensitive breast cancer cells, insulin was not growth stimulatory, likely due to the presence of hybrid InsR/IGF1R, which has high affinity for IGF-I, but not insulin. Combination inhibition of InsR and IGF1R showed complete suppression of the system in endocrine-sensitive breast cancer cells. To develop InsR-binding agents, we employed a small protein scaffold, T7 phage gene 2 protein (Gp2) with the long-term goal of creating effective InsR inhibitors and diagnostics. Using yeast display and directed evolution, we identified three Gp2 variants (Gp2 #1, #5, and #10) with low nanomolar affinity and specific binding to cell surface InsR. These Gp2 variants inhibited insulin-mediated monolayer proliferation in both endocrine-sensitive and resistant breast cancer, but did not downregulate InsR expression. Gp2 #5 and Gp2 #10 disrupted InsR function by inhibiting ligand-induced receptor activation. In contrast, Gp2 #1 did not block InsR phosphorylation. Notably, Gp2 #1 binding was enhanced by pretreatment of cells with insulin, suggesting a unique receptor-ligand-binding mode. These Gp2 variants are the first nonimmunoglobulin protein scaffolds to target insulin receptor and present compelling opportunity for modulation of InsR signaling.
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.