ArticleCancer research2013
Therapeutic destruction of insulin receptor substrates for cancer treatment.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 122 citations in OpenAlex.
- IRS-2 rs1805097 polymorphism is associated with the decreased risk of colorectal cancer.Oncotarget · 2017Pooled it
- Pooled it
- Single nucleotide polymorphisms in the IGF-IRS pathway are associated with outcome in mCRC patients enrolled in the FIRE-3 trial.International journal of cancer · 2017Trial
- CDK8/19 inhibition prevents adaptive resistance to CDK4/6 inhibitors in vitro and in vivo.Cell reports. Medicine · 2026Article
- MICAL2 as a key effector of β-catenin signaling driving melanoma progression and therapeutic resistance.Cell death and differentiation · 2026Article
- Insulin receptor substrate 2 (IRS2) confers resistance to PI3K pathway inhibition in PIK3CA mutant breast cancer.The Journal of biological chemistry · 2026Article
- EGFR-targeted affibody-polyIC polyplex kills EGFR-overexpressing cancer cells without activating the EGFR.PloS one · 2026Article
- IRS2 as a driver of brain metastasis in colorectal cancer: A potential target for novel therapeutic strategies.Neuro-oncology · 2025Article
- NT157 exhibits antineoplastic effects by targeting IRS and STAT3/5 signaling in multiple myeloma.Hematology, transfusion and cell therapy · 2024Article
- Inhibition of LAR attenuates neuroinflammation through RhoA/IRS-1/Akt signaling pathway after intracerebral hemorrhage in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Suppression of Insulin Receptor Substrate 1 Inhibits Breast Cancer Growth In Vitro and in Female Athymic Mice.Endocrinology · 2023Article
- Targeting IRS-1/2 in Uveal Melanoma Inhibits In Vitro Cell Growth, Survival and Migration, and In Vivo Tumor Growth.Cancers · 2022Article
- CirRNA circFAM126A Exerts Oncogenic Functions in NSCLC to Upregulate IRS2.Biochemical genetics · 2022Article
- RNA m6A methylation regulators in endometrial cancer (Review).International journal of oncology · 2022Article
- NT157 exerts antineoplastic activity by targeting JNK and AXL signaling in lung cancer cells.Scientific reports · 2022Article
- Renal Cell Cancer and Obesity.International journal of molecular sciences · 2022Review
- Role of PI3K/Akt/mTOR pathway in mediating endocrine resistance: concept to clinic.Exploration of targeted anti-tumor therapy · 2022Review
- Identifying the Antitumor Effects of Curcumin on Lung Adenocarcinoma Using Comprehensive Bioinformatics Analysis.Drug design, development and therapy · 2022Article
- Case report: Unique FLT4 variants associated with differential response to anlotinib in angiosarcoma.Frontiers in oncology · 2022Article
- Characterization of glucose metabolism in breast cancer to guide clinical therapy.Frontiers in surgery · 2022Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Insulin receptor substrates 1 and 2 (IRS1/2) mediate mitogenic and antiapoptotic signaling from insulin-like growth factor 1 receptor (IGF-IR), insulin receptor (IR), and other oncoproteins. IRS1 plays a central role in cancer cell proliferation, its expression is increased in many human malignancies, and its upregulation mediates resistance to anticancer drugs. IRS2 is associated with cancer cell motility and metastasis. Currently, there are no anticancer agents that target IRS1/2. We present new IGF-IR/IRS-targeted agents (NT compounds) that promote inhibitory Ser-phosphorylation and degradation of IRS1 and IRS2. Elimination of IRS1/2 results in long-term inhibition of IRS1/2-mediated signaling. The therapeutic significance of this inhibition in cancer cells was shown while unraveling a novel mechanism of resistance to B-RAF(V600E/K) inhibitors. We found that IRS1 is upregulated in PLX4032-resistant melanoma cells and in cell lines derived from patients whose tumors developed PLX4032 resistance. In both settings, NT compounds led to the elimination of IRS proteins and evoked cell death. Treatment with NT compounds in vivo significantly inhibited the growth of PLX4032-resistant tumors and displayed potent antitumor effects in ovarian and prostate cancers. Our findings offer preclinical proof-of-concept for IRS1/2 inhibitors as cancer therapeutics including PLX4032-resistant melanoma. By the elimination of IRS proteins, such agents should prevent acquisition of resistance to mutated-B-RAF inhibitors and possibly restore drug sensitivity in resistant tumors.
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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.