ArticleGut2022
PI3K-driven HER2 expression is a potential therapeutic target in colorectal cancer stem cells.
Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 97 citations in OpenAlex.
- Penfluridol directly targets PDPK1 to suppress AKT1 phosphorylation and stabilize CTR1, inducing cuproptosis in colorectal cancer.Acta pharmacologica Sinica · 2026Article
- Cancer Stem Cells in Colorectal Cancer: From Molecular Mechanisms to Diagnosis, Prognosis and Therapy Implications.Cancers · 2026Review
- The Oncogenic Role of Prostate Stem Cell Antigen (PSCA) in Colorectal Cancer: Implications for Targeted Therapy.Current issues in molecular biology · 2026Article
- EGFR-dependent delivery of phosphorylated IGFBP3 by cancer stem cells drives chemotherapy resistance in colorectal cancer.Cell death & disease · 2026Article
- Humic substances enhance the anti-cancer efficacy of standard therapies.Cell death discovery · 2026Article
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- PDIA6 promotes the cell proliferation of ESCC by enhancing the disulfide bond formation in TRAF4.Cellular & molecular biology letters · 2026Article
- Molecular profiling-directed individualized adjuvant therapy in colorectal cancer: Bridging consensus guidelines to clinical disparities.World journal of gastroenterology · 2026Review
- Novel Syngeneic Cell Lines for Studying High-Risk BRAFV600E-Driven Colorectal Cancer In Vivo.Cancer research communications · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- The resilient subset: cancer stem cells at the core of immunotherapy resistance.Immunotherapy advances · 2026Review
- Common oncogenic mutations in colorectal cancer: drivers of carcinogenesis and potential therapeutic targets.Frontiers in pharmacology · 2026Review
- Mitochondrial DNA Mutations in Colorectal Cancer Stem Cells: Implications for Tumor Dynamics and Therapeutic Strategies.Current medicinal chemistry · 2026Review
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- Valproic acid improves the efficacy of oxaliplatin/fluoropyrimidine-based chemotherapy by targeting cancer stem cell via β-Catenin modulation in colorectal cancer.Cell death & disease · 2025Article
- Comprehensive analysis of PIK3CA mutations in advanced colorectal cancer using circulating tumor DNA profiling.NPJ precision oncology · 2025Article
- HBx Drives Liver Cancer Stem Cell Generation Through Stimulating Glucose Metabolic Reprogramming.Journal of cellular and molecular medicine · 2025Article
- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- Article
- Integrative in silico and in vivo Drosophila model studies reveal the anti-inflammatory, antioxidant, and anticancer properties of red radish microgreen extract.Scientific reports · 2025Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveCancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy.
designA collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional evaluation of HER2 activation and global RNA-seq to identify the mechanisms underlying therapy resistance.
resultsHere we show that in CD44v6-positive CR-CSCs, high HER2 expression levels are associated with an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which promotes the acetylation at the regulatory elements of the Erbb2 gene. HER2 targeting in combination with phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) inhibitors induces CR-CSC death and regression of tumour xenografts, including those carrying
conclusionsWhile PI3K targeting kills liver-colonising CR-CSCs, the concomitant inhibition of PI3K, HER2 and MEK is required to induce regression of tumours resistant to anti-EGFR therapies. These data may provide a rationale for designing clinical trials in the adjuvant and metastatic setting.
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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.