ArticleOncotarget2017
Feedback activation of HER3 attenuates response to EGFR inhibitors in colon cancer cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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.
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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Association between the overexpression of Her3 and clinical pathology and prognosis of colorectal cancer: A meta-analysis.Medicine · 2018Pooled it
- Prognostic and Treatment-Specific Predictive Implications of HER2 Expression in RAS Wild-Type Metastatic Colorectal Cancer: A Multicenter Retrospective Real-World Study.Journal of clinical medicine · 2026Article
- Inhibition of colorectal cancer progression through conformation-specific targeting of ADAM10 metalloprotease.Frontiers in oncology · 2025Article
- Potential Drug Synergy Through the ERBB2 Pathway in HER2+ Breast Tumors.International journal of molecular sciences · 2024Article
- Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells.British journal of cancer · 2024Article
- ESM1 facilitates the EGFR/HER3-triggered epithelial-to-mesenchymal transition and progression of gastric cancer via modulating interplay between Akt and angiopoietin-2 signaling.International journal of biological sciences · 2024Article
- Review
- Article
- MiR-323a regulates ErbB3/EGFR and blocks gefitinib resistance acquisition in colorectal cancer.Cell death & disease · 2022Article
- LncRNAs, the Molecules Involved in Communications With Colorectal Cancer Stem Cells.Frontiers in oncology · 2022Review
- Article
- A phospho-proteomic study of cetuximab resistance in KRAS/NRAS/BRAFCellular oncology (Dordrecht, Netherlands) · 2021Article
- HER2-HER3 Heterodimer Quantification by FRET-FLIM and Patient Subclass Analysis of the COIN Colorectal Trial.Journal of the National Cancer Institute · 2020Article
- Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype.Science translational medicine · 2020Article
- MiR-519d targets HER3 and can be used as a potential serum biomarker for non-small cell lung cancer.Aging · 2020Article
- The novel long noncoding RNA CRART16 confers cetuximab resistance in colorectal cancer cells by enhancing ERBB3 expression via miR-371a-5p.Cancer cell international · 2020Article
- Broad-spectrum receptor tyrosine kinase inhibitors overcomeOncotarget · 2019Article
- Imaging EGFR and HER3 throughScientific reports · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
The EGFR inhibitor cetuximab is approved for the treatment of colorectal cancer. However, both innate and acquired resistance mechanisms, including compensatory feedback loops, limit its efficacy. Nevertheless, the emergence of these feedback loops has remained largely unexplored to date. Here, we showed feedback upregulation of HER3 and induction of HER3 phosphorylation after cetuximab treatment in colon cancer cells. We also showed that this upregulation occurs, at least partly, through AKT inhibition. Together with this, we observed increased HER2:HER3 dimerization upon cetuximab treatment. Interestingly, lapatinib, a dual EGFR and HER2 tyrosine kinase inhibitor, blocked the increase of cetuximab-induced HER3 phosphorylation. Additionally, we showed that upon HER3 knockdown, cetuximab combined with lapatinib was able to decrease cell viability compared to HER3 expressing cells. These results suggest the existence of a cetuximab-induced feedback HER3 activation that could potentially result in reduced cetuximab efficacy in colorectal cancer patients. Taken together, we provide evidence of the limited effectiveness of cetuximab monotherapy compared to rational combinations.
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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.