ArticleNeuro-oncology2025
IRS2 as a driver of brain metastasis in colorectal cancer: A potential target for novel therapeutic strategies.
Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis 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.
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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
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- IRS2 as a driver and therapeutic target in brain metastases from colorectal cancer: a systematic review of mechanistic and translational evidence.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Pooled it
- Development and validation of a ferroptosis-related gene signature for prognostic prediction and therapeutic target identification in invasive lobular carcinoma.Translational cancer research · 2026Article
- High resolution genome-wide SNP array analyses on matched colorectal-based lung and brain metastases.Journal of cancer research and clinical oncology · 2026Article
- Bacterial extracellular vesicles in colorectal cancer: mechanisms, biomarker potential, and therapeutic engineering.Cell communication and signaling : CCS · 2026Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
backgroundColorectal cancer (CRC) ranks as the fourth most common cause of brain metastasis (BM), with its incidence on the rise. However, the molecular mechanisms driving the formation of these lesions from CRC remain unclear.
methodsWe analyzed the Foundation Medicine genomic database, which includes over 35,000 CRC samples from both local and metastatic sites. The role of insulin receptor substrate 2 (IRS2) in CRC brain tropism was investigated using various in vitro (co-culture systems and 3D sphere formation assays), in vivo (intracranial and subcutaneous mouse models), and ex vivo (CRC Patient-Derived Explants) models. The molecular and metabolic effects of IRS2 were examined through RNA sequencing and Seahorse analysis. The therapeutic potential of a combined treatment with NT219, an IRS2 inhibitor, and 5-fluorouracil (5-FU) was assessed using our CRC BM mouse model.
resultsOur research reveals a distinctive genomic profile of CRC BM and highlights the role of IRS2 in promoting CRC BM. IRS2 mediates its effect by modulating the β-catenin and oxidative phosphorylation (OXPHOS) pathways. We developed a mouse model of BM from CRC and demonstrated that treatment with the IRS2 inhibitor NT219, in combination with 5-FU, significantly suppresses BM development and prolongs survival.
conclusionsOur work underscores the unique role of IRS2 in facilitating CRC brain adaptation and suggests a novel therapeutic strategy for CRC patients with BM.
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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.