ArticleCell cycle (Georgetown, Tex.)2014
Activities of multiple cancer-related pathways are associated with BRAF mutation and predict the resistance to BRAF/MEK inhibitors in melanoma cells.
Article in Cell cycle (Georgetown, Tex.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Defective biological networks associated with pseudogene-derived lncRNAs in cancer drug resistance: Promising prospects for their clinical targets in cancer therapy.Genes & diseases · 2026Review
- Molecular Basis of BRAF Inhibitor Resistance in Melanoma: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Lamivudine, Doravirine, and Cabotegravir Downregulate the Expression of Human Endogenous Retroviruses (HERVs), Inhibit Cell Growth, and Reduce Invasive Capability in Melanoma Cell Lines.International journal of molecular sciences · 2024Article
- Hyperforin Enhances Heme Oxygenase-1 Expression Triggering Lipid Peroxidation in BRAF-Mutated Melanoma Cells and Hampers the Expression of Pro-Metastatic Markers.Antioxidants (Basel, Switzerland) · 2023Article
- Salviolone fromInternational journal of molecular sciences · 2022Article
- PTENP1-AS contributes to BRAF inhibitor resistance and is associated with adverse clinical outcome in stage III melanoma.Scientific reports · 2021Article
- Many Distinct Ways Lead to Drug Resistance inLife (Basel, Switzerland) · 2021Review
- Proof-of-Concept Study of Multifunctional Hybrid Nanoparticle System Combined with NIR Laser Irradiation for the Treatment of Melanoma.Biomolecules · 2021Article
- Basal-like breast cancer with low TGFβ and high TNFα pathway activity is rich in activated memory CD4 T cells and has a good prognosis.International journal of biological sciences · 2021Article
- Association of an anaplastic lymphoma kinase pathway signature with cell de-differentiation, neoadjuvant chemotherapy response, and recurrence risk in breast cancer.Cancer communications (London, England) · 2020Article
- AR pathway activity correlates with AR expression in a HER2-dependent manner and serves as a better prognostic factor in breast cancer.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Commonly integrated epigenetic modifications of differentially expressed genes lead to adaptive resistance in cancer.Epigenomics · 2019Article
- Concomitant dysregulation of the estrogen receptor and BRAF/MEK signaling pathways is common in colorectal cancer and predicts a worse prognosis.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- P21-activated kinase 1 regulates resistance to BRAF inhibition in human cancer cells.Molecular carcinogenesis · 2017Article
- Antiangiogenic antibody improves melanoma detection by fluorescently labeled therapeutic antibodies.The Laryngoscope · 2016Article
- REC8 is a novel tumor suppressor gene epigenetically robustly targeted by the PI3K pathway in thyroid cancer.Oncotarget · 2015Article
- Estrogen Receptor β Agonists Differentially Affect the Growth of Human Melanoma Cell Lines.PloS one · 2015Article
- c-Myc modulation: a key role in melanoma drug response.Cancer biology & therapy · 2015Article
- AurkA inhibitors enhance the effects of B-RAF and MEK inhibitors in melanoma treatment.Journal of translational medicine · 2014Article
- PCTAIRE1 regulates p27 stability, apoptosis and tumor growth in malignant melanoma.Oncoscience · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Drug resistance is a major obstacle in the targeted therapy of melanoma using BRAF/MEK inhibitors. This study was to identify BRAF V600E-associated oncogenic pathways that predict resistance of BRAF-mutated melanoma to BRAF/MEK inhibitors. We took in silico approaches to analyze the activities of 24 cancer-related pathways in melanoma cells and identify those whose activation was associated with BRAF V600E and used the support vector machine (SVM) algorithm to predict the resistance of BRAF-mutated melanoma cells to BRAF/MEK inhibitors. We then experimentally confirmed the in silico findings. In a microarray gene expression dataset of 63 melanoma cell lines, we found that activation of multiple oncogenic pathways preferentially occurred in BRAF-mutated melanoma cells. This finding was reproduced in 5 additional independent melanoma datasets. Further analysis of 46 melanoma cell lines that harbored BRAF mutation showed that 7 pathways, including TNFα, EGFR, IFNα, hypoxia, IFNγ, STAT3, and MYC, were significantly differently expressed in AZD6244-resistant compared with responsive melanoma cells. A SVM classifier built on this 7-pathway activation pattern correctly predicted the response of 10 BRAF-mutated melanoma cell lines to the MEK inhibitor AZD6244 in our experiments. We experimentally showed that TNFα, EGFR, IFNα, and IFNγ pathway activities were also upregulated in melanoma cell A375 compared with its sub-line DRO, while DRO was much more sensitive to AZD6244 than A375. In conclusion, we have identified specific oncogenic pathways preferentially activated in BRAF-mutated melanoma cells and a pathway pattern that predicts resistance of BRAF-mutated melanoma to BRAF/MEK inhibitors, providing novel clinical implications for melanoma therapy.
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