ArticleOncotarget2017
ATM mutations and E-cadherin expression define sensitivity to EGFR-targeted therapy in colorectal cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
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- Genetic profiling of osteosarcoma in an adolescent using a next‑generation sequencing panel and Sanger sequencing: A case report and review of the literature.Biomedical reports · 2025Article
- Role of Cell-Cell Junctions in Oesophageal Squamous Cell Carcinoma.Biomolecules · 2022Review
- E-cadherin is a robust prognostic biomarker in colorectal cancer and low expression is associated with sensitivity to inhibitors of topoisomerase, aurora, and HSP90 in preclinical models.Molecular oncology · 2022Article
- EGFR Protein Expression Relates with Tumor Histology, Methylation Status of EGFR and HPV16 E6 Viral Load in Oropharyngeal Carcinoma.Head and neck pathology · 2021Article
- Multi gene mutation signatures in colorectal cancer patients: predict for the diagnosis, pathological classification, staging and prognosis.BMC cancer · 2021Article
- Transitioning the Molecular Tumor Board from Proof of Concept to Clinical Routine: A German Single-Center Analysis.Cancers · 2021Article
- Tumor Inhibitory Effect of Long Non-coding RNA LOC100505817 on Gastric Cancer.Pathology oncology research : POR · 2021Article
- Modeling Adaptive Resistance of KRAS Mutant Colorectal Cancer to MAPK Pathway Inhibitors with a Three-Dimensional Tumor Model.ACS pharmacology & translational science · 2020Article
- Article
- Overcoming malignant cell-based mechanisms of resistance to immune checkpoint blockade antibodies.Seminars in cancer biology · 2020Review
- Molecular characterization of colorectal cancer using whole-exome sequencing in a Taiwanese population.Cancer medicine · 2019Article
- Andrographolide induces DNA damage in prostate cancer cells.Oncotarget · 2019Article
- Anti-claudin-4 extracellular domain antibody enhances the antitumoral effects of chemotherapeutic and antibody drugs in colorectal cancer.Oncotarget · 2018Article
- Review
- Personalized Clinical Decision Making Through Implementation of a Molecular Tumor Board: A German Single-Center Experience.JCO precision oncology · 2018Article
- Next-generation sequencing: recent applications to the analysis of colorectal cancer.Journal of translational medicine · 2017Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
EGFR-targeted therapy is a key treatment approach in patients with RAS wildtype metastatic colorectal cancers (CRC). Still, also RAS wildtype CRC may be resistant to EGFR-targeted therapy, with few predictive markers available for improved stratification of patients. Here, we investigated response of 7 CRC cell lines (Caco-2, DLD1, HCT116, HT29, LS174T, RKO, SW480) to Cetuximab and correlated this to NGS-based mutation profiles, EGFR promoter methylation and EGFR expression status as well as to E-cadherin expression. Moreover, tissue specimens of primary and/or recurrent tumors as well as liver and/or lung metastases of 25 CRC patients having received Cetuximab and/or Panitumumab were examined for the same molecular markers. In vitro and in situ analyses showed that EGFR promoter methylation and EGFR expression as well as the MSI and or CIMP-type status did not guide treatment responses. In fact, EGFR-targeted treatment responses were also observed in RAS exon 2 p.G13 mutated CRC cell lines or CRC cases and were further linked to PIK3CA exon 9 mutations. In contrast, non-response to EGFR-targeted treatment was associated with ATM mutations and low E-cadherin expression. Moreover, down-regulation of E-cadherin by siRNA in otherwise Cetuximab responding E-cadherin positive cells abrogated their response. Hence, we here identify ATM and E-cadherin expression as potential novel supportive predictive markers for EGFR-targeted therapy.
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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.