ArticleOncotarget2015
ErbB-3 activation by NRG-1β sustains growth and promotes vemurafenib resistance in BRAF-V600E colon cancer stem cells (CSCs).
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Resistance of Colorectal Cancer Stem Cells to Modern Therapies: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- HER3-targeting Antibody-drug Conjugates Therapy for Solid Tumors: Recent Advances and Future Potentials.Current medicinal chemistry · 2026Review
- Resistance to antibody-drug conjugates: A review.Acta pharmaceutica Sinica. B · 2025Review
- CTHRC1 is associated withBiomolecules & biomedicine · 2024Article
- Prevalence of HER3 Expression in Pancreatic Cancer Patients Treated With Systemic Chemotherapy.Cancer medicine · 2024Article
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Review
- Review
- Thirty Years of HER3: From Basic Biology to Therapeutic Interventions.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Review
- EV20/NMS-P945, a Novel Thienoindole Based Antibody-Drug Conjugate Targeting HER-3 for Solid Tumors.Pharmaceutics · 2021Article
- MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Cancer Stem Cells-Key Players in Tumor Relapse.Cancers · 2021Review
- Antibody-Drug Conjugates: The New Frontier of Chemotherapy.International journal of molecular sciences · 2020Review
- HER3 targeting with an antibody-drug conjugate bypasses resistance to anti-HER2 therapies.EMBO molecular medicine · 2020Article
- Tumor cell sensitivity to vemurafenib can be predicted from protein expression in a BRAF-V600E basket trial setting.BMC cancer · 2019Article
- Article
- Review
- HER3 signaling and targeted therapy in cancer.Oncology reviews · 2018Article
- EV20-Sap, a novel anti-HER-3 antibody-drug conjugate, displays promising antitumor activity in melanoma.Oncotarget · 2017Article
- A comprehensive review of heregulins, HER3, and HER4 as potential therapeutic targets in cancer.Oncotarget · 2017Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Approximately 5-10% of metastatic colorectal cancers harbor a BRAF-V600E mutation, which is correlated with resistance to EGFR-targeted therapies and worse clinical outcome. Vice versa, targeted inhibition of BRAF-V600E with the selective inhibitor PLX 4032 (Vemurafenib) is severely limited due to feedback re-activation of EGFR in these tumors. Mounting evidence indicates that upregulation of the ErbB-3 signaling axis may occur in response to several targeted therapeutics, including Vemurafenib, and NRG-1β-dependent re-activation of the PI3K/AKT survival pathway has been associated with therapy resistance.Here we show that colon CSCs express, next to EGFR and ErbB-2, also significant amounts of ErbB-3 on their membrane. This expression is functional as NRG-1β strongly induces AKT/PKB and ERK phosphorylation, cell proliferation, clonogenic growth and promotes resistance to Vemurafenib in BRAF-V600E mutant colon CSCs. This resistance was completely dependent on ErbB-3 expression, as evidenced by knockdown of ErbB-3. More importantly, resistance could be alleviated with therapeutic antibody blocking ErbB-3 activation, which impaired NRG-1β-driven AKT/PKB and ERK activation, clonogenic growth in vitro and tumor growth in xenograft models. In conclusion, our findings suggest that targeting ErbB-3 receptors could represent an effective therapeutic approach in BRAF-V600E mutant colon cancer.
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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.