ArticleJournal of translational medicine2017
Identification of coexistence of BRAF V600E mutation and EZH2 gain specifically in melanoma as a promising target for combination therapy.
Article in Journal of translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 37 citations in OpenAlex.
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- New Approaches to Targeted Therapy in Melanoma.Cancers · 2023Review
- Resistance to BRAF Inhibitors: EZH2 and Its Downstream Targets as Potential Therapeutic Options in Melanoma.International journal of molecular sciences · 2023Article
- lncRNAs-EZH2 interaction as promising therapeutic target in cutaneous melanoma.Frontiers in molecular biosciences · 2023Review
- Identification of hepatocellular carcinoma subtypes based on PcG-related genes and biological relevance with cancer cells.Clinical epigenetics · 2022Article
- Drugging the Epigenome: Overcoming Resistance to Targeted and Immunotherapies in Melanoma.JID innovations : skin science from molecules to population health · 2022Review
- The pleiotropic roles of circular and long noncoding RNAs in cutaneous melanoma.Molecular oncology · 2022Review
- Synthesis, structure andRSC advances · 2021Article
- RePhine: An Integrative Method for Identification of Drug Response-related Transcriptional Regulators.Genomics, proteomics & bioinformatics · 2021Article
- Predictive biomarkers and potential drug combinations of epi-drugs in cancer therapy.Clinical epigenetics · 2021Review
- MicroRNA-205-5p inhibits skin cancer cell proliferation and increase drug sensitivity by targeting TNFAIP8.Scientific reports · 2021Article
- A Melanoma-Tailored Next-Generation Sequencing Panel Coupled with a Comprehensive Analysis to Improve Routine Melanoma Genotyping.Targeted oncology · 2020Article
- Non-BRAF Mutant Melanoma: Molecular Features and Therapeutical Implications.Frontiers in molecular biosciences · 2020Review
- Epigenetic heterogeneity in cancer.Biomarker research · 2019Review
- The Role of Ketogenic Diet in the Treatment of Neuroblastoma.Integrative cancer therapiesReview
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCoexistence of enhancer of zeste homolog 2 (EZH2) and BRAF gene aberrations has been described in many cancer types. In this study, we aim to explore the coexistence status of BRAF V600E mutation and the copy number variation of EZH2 and explore the potential of this combination as a therapeutic target.
methodsA total of 138 cases of melanoma samples harboring BRAF V600E mutation were included, and EZH2 copy numbers were examined by QuantiGenePlex DNA Assays. Clinical pathological distinction between patient groups with or without EZH2 amplification (hereafter referred to as EZH2 gain) was statistically analyzed. The sensitivity of melanoma cell lines and patient-derived xenograft (PDX) models containing BRAF V600E mutation with or without EZH2 gain to vemurafenib (BRAF inhibitor), GSK2816126 (EZH2 inhibitor) and a combination of both agents was evaluated.
resultsIn our cohort, the coexistence rate of BRAF V600E mutation and EZH2 gain was up to 29.0%, and significant differences in overall survival and disease-free survival were found between no EZH2 copy number gain and gain groups (P = 0.038, P = 0.030), gain and high EZH2 copy number gain groups (P = 0.006, P = 0.010). Combination with BRAF and EZH2 inhibition showed better inhibitory efficacy in melanoma prevention compared with vemurafenib monotherapy. More importantly, this improved therapeutic effect was observed especially in melanoma cell lines and PDX models containing concurrently BRAF V600E mutation and EZH2 gain.
conclusionsCoexistence of BRAF V600E mutation and EZH2 gain is rather prevalent in melanoma. Our findings provided evidence for the feasibility of combination therapy with EZH2 and BRAF inhibitors in melanoma with concurrent BRAF V600E mutation and EZH2 gain.
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