ArticleOncotarget2015
Combination of antibodies directed against different ErbB3 surface epitopes prevents the establishment of resistance to BRAF/MEK inhibitors in melanoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2.International journal of molecular sciences · 2023Review
- HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022Review
- Review
- In Vitro Biophysical and Biological Characterization of Lipid Nanoparticles Co-Encapsulating Oncosuppressors miR-199b-5p and miR-204-5p as Potentiators of Target Therapy in Metastatic Melanoma.International journal of molecular sciences · 2020Article
- Article
- Single cell analysis to dissect molecular heterogeneity and disease evolution in metastatic melanoma.Cell death & disease · 2019Review
- Article
- ITCH-dependent proteasomal degradation of c-FLIP induced by the anti-HER3 antibody 9F7-F11 promotes DR5/caspase 8-mediated apoptosis of tumor cells.Cell communication and signaling : CCS · 2019Article
- Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma.Cell death and differentiation · 2019Article
- Inhibition of Stearoyl-CoA desaturase 1 reverts BRAF and MEK inhibition-induced selection of cancer stem cells in BRAF-mutated melanoma.Journal of experimental & clinical cancer research : CR · 2018Article
- HMGA1/E2F1 axis and NFkB pathways regulate LPS progression and trabectedin resistance.Oncogene · 2018Article
- Therapeutic potential of combined BRAF/MEK blockade in BRAF-wild type preclinical tumor models.Journal of experimental & clinical cancer research : CR · 2018Article
- Characterising the phenotypic evolution of circulating tumour cells during treatment.Nature communications · 2018Article
- BRAF inhibition upregulates a variety of receptor tyrosine kinases and their downstream effector Gab2 in colorectal cancer cell lines.Oncogene · 2018Article
- Dual targeting of HER3 and MEK may overcome HER3-dependent drug-resistance of colon cancers.Oncotarget · 2017Article
- MicroRNAs in melanoma development and resistance to target therapy.Oncotarget · 2017Review
- The natural compound fucoidan from New Zealand Undaria pinnatifida synergizes with the ERBB inhibitor lapatinib enhancing melanoma growth inhibition.Oncotarget · 2017Article
- Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015.Journal of translational medicine · 2016Article
- MITF depletion elevates expression levels of ERBB3 receptor and its cognate ligand NRG1-beta in melanoma.Oncotarget · 2016Article
- miR-579-3p controls melanoma progression and resistance to target therapy.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients with metastatic melanoma bearing V600 mutations in BRAF oncogene clinically benefit from the treatment with BRAF inhibitors alone or in combination with MEK inhibitors. However, a limitation to such treatment is the occurrence of resistance. Tackling the adaptive changes helping cells survive from drug treatment may offer new therapeutic opportunities. Very recently the ErbB3 receptor has been shown to act as a central node promoting survival of BRAF mutated melanoma. In this paper we first demonstrate that ErbB3/AKT hyperphosphorylation occurs in BRAF mutated melanoma cell lines following exposure to BRAF and/or MEK inhibitors. This strongly correlates with increased transcriptional activation of its ligand neuregulin. Anti-ErbB3 antibodies impair the establishment of de novo cell resistance to BRAF inhibition in vitro. In order to more potently ablate ErbB3 activity we used a combination of two anti-ErbB3 antibodies directed against distinct epitopes of its extracellular domain. These two antibodies in combo with BRAF/MEK inhibitors potently inhibit in vitro cell growth and tumor regrowth after drug withdrawal in an in vivo xenograft model. Importantly, residual tumor masses from mice treated by the antibodies and BRAF/ERK inhibitors combo are characterized almost exclusively by large necrotic areas with limited residual areas of tumor growth. Taken together, our findings support the concept that triple therapy directed against BRAF/MEK/ErbB3 may be able to provide durable control of BRAF mutated metastatic melanoma.
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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.